Category: 3. Business

Guest lecture by Piero Cipollone, Member of the Executive Board of the ECB, at the Frankfurt School of Finance & Management

Frankfurt am Main, 8 December 2025

Money is at the heart of what central banks do.^[1] Ever since central banks have existed, their fundamental role has been to issue money and protect its value. This role has been the same for centuries, and I don’t expect it to change. But what is changing is the environment in which central banks must deliver on this mandate. There are obviously many sides to this, but today I will focus on technology.

Digital payments are the new normal. And new technologies have emerged that are disrupting financial services, leading us to rethink their future. We are facing no less than a paradigm shift. Financial institutions have become technological entities. At the same time, tech firms have entered the realms of payments and finance. In fact, financial institutions and tech firms have all become fintechs. What was once a niche has become the norm. Harnessing technology to provide better financial services is now the name of the game.

Central banks are no exception. If they are to retain their role in issuing money that is fit for purpose, they have to embrace technology and shape the transformation of money. Adapting to new technologies is not an option, it is an existential must. If central banks don’t issue digital money, they will lose their central role in money issuance and fail to provide an anchor of stability to the entire financial system. Central banks are increasingly becoming tech organisations; they must evolve with technology, or risk falling behind.

Today, I will argue that in the European context, the central bank needs to not just follow but take a leading role in this transformation. If it doesn’t, Europe risks failing to leverage its collective strength. This is because financial integration is key to achieving the network effects and economies of scale required to enable our economy and financial sector to reap the benefits of these new technologies while mitigating their risks. This is particularly vital for the European Central Bank, which operates in a monetary union, where the singleness of money across the union is necessary for the smooth functioning of payments and the effective transmission of monetary policy. Looking ahead, we also need to ensure the singleness of digital money. Doing so will provide a Europe-wide ecosystem in which the private sector can compete by offering, and scaling up, innovative new services.

We can build on strong foundations. Over the past 25 years, the euro has become the currency of 20 member countries, with Bulgaria set to become the 21st euro area member next month. The euro has established itself firmly as the world’s second most important currency. The Eurosystem – that is, the ECB and the national central banks of euro area countries – implements a single monetary policy that safeguards the value of the euro and sustains the trust Europeans place in their money.

We have built robust market infrastructures that underpin the euro. T2 (for large-value payments), T2S (for securities) and TIPS (for instant payments) make it possible to settle in central bank money, a risk-free asset. Together with ECMS (for collateral management), these public payment rails allow money, securities and collateral to move freely, safely and efficiently across the euro area. Seen from where we were 25 years ago, the degree of integration achieved in just over two decades is remarkable.

However, we still face three key challenges.

First, fragmentation persists for retail payments. While the Single Euro Payments Area (SEPA) has provided a pan-European solution for credit transfers and direct debits, we have not achieved the same result at the point of interaction.^[2] Despite infrastructures like TIPS enabling instant payments across the euro area and the encouragement of the Eurosystem, we still lack a European solution that can be used to pay digitally throughout the euro area for all use cases. This has resulted in an excessive dependency on non-European providers for critical retail payment services like cards and digital wallets. This raises fundamental questions about our strategic autonomy, as this dependency could potentially be used against us as an instrument of economic coercion.

Second, the very nature of money and payments is changing in ways that could undermine the balance that has underpinned monetary stability in Europe. The emergence of new technologies, such as tokenisation and distributed ledger technology (DLT)^[3], has the potential to enhance efficiency in capital markets. But in the absence of tokenised central bank money, the new ecosystem would not have a common risk-free settlement asset at its core. The lack of the latter could undo the progress achieved in wholesale payments between financial institutions by reintroducing fragmentation and credit risk, while creating new dependencies. Moreover, the expansion of alternative settlement assets denominated in foreign currencies would go against the objectives of the savings and investments union and undermine monetary sovereignty. This would also challenge the balance between public and private money that has served us well so far, with public money providing an anchor of stability into which all private assets can be converted.

Third, cross-border payments have been a lingering challenge. Because they remain slow and expensive, the race is on to make them more efficient. While this is a possible use case for stablecoins, the latter create a number of risks for domestic currencies and financial systems. They could also threaten the international role of the euro if no strong European alternative emerges to challenge the currently dominant dollar-denominated stablecoins.

In this context, inaction is not the best choice for Europe. Doing nothing could lead to central bank money becoming increasingly marginalised, which could end up challenging the resilience of our payments system and undermining the stability of our financial system, our monetary sovereignty, our strategic autonomy and our economic security. Over time, this could also weaken the competitive position of European financial institutions and infrastructures, which, given their importance for the financing of the economy, could in turn weigh on European productivity. And it could diminish the role of the euro on the global stage.

Our mandate does not allow us to take these risks lightly. When the foundations of money and payments are shifting along with technology, the central bank cannot stand still. We must modernise our payments offering so that it evolves alongside technological progress and supports the development of an integrated European market for digital payments and digital assets. Our goal is not to replace private innovation but to provide a solid public foundation that will enable the private sector to innovate at scale while avoiding excessive dependencies.

This requires a reinvigorated public-private partnership across three payment dimensions: retail, wholesale and cross-border. In my remarks today, I will outline our overall approach and then explain our strategy for retail payments (with the issuance of a digital equivalent of cash, the digital euro), wholesale payments (by making it possible to settle DLT-based transactions in central bank money) and cross-border payments (with the interlinking of fast payment systems).

A public-private partnership anchored in central bank money

The complementarity of public and private money

The Eurosystem’s starting point is its core responsibility as an issuer of money and guardian of the smooth functioning of payment systems. In practice, this means offering means of payment for retail and wholesale transactions, while ensuring that payment systems remain safe and resilient.

This has several implications.

First, central bank money is a key pillar of our financial system, and we have a duty to keep it fit for purpose as technologies and preferences evolve.^[4] It cannot be merely a niche solution for specific use cases or a dispensable add-on; it must respond to the evolving needs of people, businesses and market participants.

Second, we want to see a strong European payments ecosystem, where the private sector can provide robust, efficient and innovative solutions that can be scaled up.

These two objectives are not contradictory. In fact, they have strong synergies.

Central bank money solutions are based on pan-European infrastructures and standards that the private sector can leverage. This not only reduces the risk of fragmentation and ensures interoperability, but also avoids the need for the private sector to duplicate investments, and reduces costs for the system as a whole. This is particularly important in a sector characterised by network effects, where technological dominance and proprietary standards can otherwise restrict the ability of others to compete, innovate and scale up, as is currently the case in digital retail payments.

Another complementarity stems from the characteristic of central bank money as a settlement asset free of credit and liquidity risk, issued by an institution that can deliver finality and stability, even under stress. Some fear that this may create the perception that private money is unsafe. I think the opposite is true. It is the very existence of central bank money as a safe asset and the convertibility of private money at par at all times that gives people confidence when using private money. That is what makes a euro a euro across instruments, institutions and technologies. On the rare occasions when this relationship was broken – in the Free Banking Era in the United States^[5], for example – financial instability ensued. Experimenting without central bank money for retail or wholesale payments would be unwise.

In fact, in the wholesale space, this is a key reason why the private sector has explicitly told us that the absence of central bank money as a settlement asset is a major impediment to the growth of the digital assets ecosystem. Today, wholesale settlement in the euro area is already digital and in central bank money. But innovation is moving into new environments: tokenised securities, DLT-based trading and settlement, and smart contract automation. If we want these innovations to be scaled up safely in Europe, central bank money has clear advantages in terms of safety, scalability and liquidity management compared with private settlement assets constrained by reserves backing and market risk.^[6]

In other words, central bank money guarantees the availability of a European settlement solution covering the euro area as a whole, ensuring the singleness of money and strengthening resilience. At the same time, it provides common rails that create a level playing field and a safe basis for the private sector to compete and innovate on functionality, user experience, value-added services and business models.

A collaborative approach

To leverage public-private synergies, our approach is explicitly collaborative. We actively engage with all stakeholders, for instance in the context of the Euro Retail Payments Board and our advisory groups on market infrastructures.^[7] We also conduct tests in conjunction with the market rather than building solutions in isolation. Let me give you two examples.

First, in the retail space, we set up a digital euro innovation platform to explore innovations and applications that the digital euro could enable. The first round involved almost 70 participants – including merchants, fintech companies, start-ups, academia, banks and other payment service providers.^[8] Market participants identified conditional payments, i.e. payments that are triggered automatically when predefined conditions are met, as a key driver of innovation. Using the digital euro’s standards and its reservation of funds functionality – which would allow money to be set aside while a payment is in progress – payment service providers could offer conditional payments throughout the euro area that go far beyond what is available today. In online shopping transactions, for example, funds could be released to the seller only after the buyer confirms delivery. Reimbursements could be automated and, in the case of delayed services, refunds could be streamlined. Payment service providers would also be able to automate business-to-business payment flows in a standardised way, helping to speed up payments, reduce paperwork and cut costs.

Second, in wholesale markets, the Eurosystem conducted extensive exploratory work in 2024 on settling DLT-based transactions in central bank money. Some 64 participants were involved in real and mock transactions covering a wide range of securities and payments use cases.^[9] With a total of €1.6 billion settled over a six-month period, this was the largest and most comprehensive exploratory work on wholesale DLT settlement in the world to date.

Technology neutrality

In adapting our offering of central bank money and supporting the digital transformation of financial services, we are technology neutral. We are not picking winners.

In retail, offering cash in both physical and digital form is in itself an example – and even a condition – of technology neutrality. It avoids limiting the choice of paying in central bank money to the payment format. This supports consumers’ freedom of choice. Discriminating against central bank money in digital payments would, on the contrary, reduce this freedom.

Another example of technology neutrality is that we are designing the digital euro to remain open to new technologies. Take privacy, for instance. The digital euro is designed to make privacy a priority, not least by offering an offline functionality that will offer cash-like privacy. And for online payments, the Eurosystem will only see encrypted codes for the payer and the payee. We will not see any personal information. Moreover, we are committed to keep using the most advanced privacy-enhancing technologies suitable for a system that must reliably and instantaneously process a considerable number of transactions every day.

In wholesale markets, we may see a future where DLT is used in some segments, traditional databases in others, with hybrid architectures in many cases. Our objective is not to oblige market participants to use a particular technological stack, but to ensure that whichever technology they adopt, the system remains safe, integrated and resilient by being connected to central bank money. This is why we will offer central bank money settlement for both DLT-based and traditional transactions. We are also neutral towards private business models and actors, provided they operate within a robust regulatory perimeter. Market participants should be able to innovate, but they must respect prudential and conduct requirements and meet expectations for anti-money laundering and countering the financing of terrorism.

The digital euro: establishing a European solution and a single market for everyday retail payments

Having presented the key pillars of our approach, namely complementarity between public and private money, public-private collaboration and technology neutrality, let me now discuss in more detail what this approach entails for retail, wholesale and cross-border payments.

In retail payments, the digital euro will ensure all Europeans can use a European solution to pay throughout the euro area, in shops, in ecommerce and from person to person. At the same time, the digital euro will establish a single market for everyday retail payments by making it much easier for providers to scale up private European solutions.

A digital equivalent of cash

For decades, cash has provided a universal means of payment that everyone could use for most payments, thanks to its legal tender status. But as commerce becomes increasingly digital – with online payments, for instance, now accounting for one-third of day-to-day transactions – the use of cash is declining.

In the absence of an equivalent public option in the digital sphere, the gap has been filled by a few mostly non-European solutions. International card schemes account for two-thirds of card transactions in the euro area. Out of 20 euro area countries, 13 do not even have a domestic card payment solution.

This situation cannot be solved through the interoperability of existing domestic solutions. While such interoperability can help address some challenges, it does not create domestic solutions where they do not exist, nor does it allow existing domestic solutions to expand to use cases they do not currently cover. Interoperability requires each participant to develop functionalities in parallel. This increases costs and complexity, hindering scalability.

The digital euro would be fundamentally new in the European context. It would provide a European digital means of payment in central bank money that would have legal tender status and would thus be accepted throughout the euro area wherever one can pay digitally. For consumers, it would extend the benefits of cash to the digital sphere. And for merchants, it would reduce costs compared with the dominant international payment solutions, both directly and indirectly by increasing merchants’ negotiating power.

Preserving the role of banks in financing the economy

The digital euro has been designed to preserve the role of banks in the financing of the economy. In the euro area, banks assume a key role in this regard and thus in the transmission of monetary policy. We have no intention of disrupting this role. In fact, the digital euro will protect it.

Banks will be at the centre of the digital euro distribution; they will keep the customer relationship and manage the digital euro accounts. This will allow them to retain data that are crucial for assessing the creditworthiness of their clients and thus for their role in financing the economy. And we will prepare with banks so that they are ready to distribute the digital euro. In 2027 we plan to launch a pilot offering banks an opportunity to gain first-hand experience in a simulated digital euro ecosystem. This pilot will not only provide the Eurosystem with valuable insights, but will also allow banks to provide feedback.^[10]

Moreover, the digital euro will allow banks to be compensated (they will continue receiving fees), while no longer having to pay the fees charged by international card schemes (as the Eurosystem will cover scheme and settlement costs).

And by offering a convenient payment solution, the digital euro will reduce the risk that the banks’ customers turn to alternatives. This will reduce the risk of deposit outflows to stablecoins, which could soon represent an alternative to banks as the source of funds for payments with cards and mobile solutions.

Several safeguards have been included in the design of the digital euro to ensure it does not disintermediate banks. First, the digital euro will not be remunerated. Second, a link to their commercial bank account will allow consumers to pay amounts that exceed their digital euro holdings, thereby reducing their incentive to keep high digital euro holdings in the first place. And third, digital euro holding limits will avoid any destabilising deposit outflows.^[11]

A springboard for European private solutions to expand

Moreover, the digital euro is a major opportunity for European payment service providers, including banks.

First, co-badging with digital euro would allow existing European payment solutions to expand their reach, without losing transactions for which they are already accepted.^[12] This applies to both physical cards and digital wallets.

Second, the digital euro would provide a single standard across Europe with unparalleled coverage given the digital euro’s legal tender status. Using this standard would significantly reduce the cost of expanding the acceptance network of European payment solutions. We have been working on this standard with market participants as part of the Rulebook Development Group.^[13] This standard could be made available shortly after the legislation is adopted and merchants would start to use it even before the digital euro’s launch, as they seek to be “digital euro-ready” when updating their payment terminals.

Third, the digital euro would allow banks to offer new, innovative payment services at scale, for instance using the reservation of funds functionality as I explained earlier.

Overall, this could make it much easier for current European private initiatives to achieve their objectives, whether they are based on cross-border integration like Wero or interoperability like EuroPA. I believe there is no dichotomy between the digital euro and European private initiatives, but instead complementarities and synergies.

To reap these synergies, it is crucial that the digital euro and European private initiatives progress in parallel. By aligning on digital euro standards, while making maximum use of existing standards and building on established infrastructures as much as possible, costs will be minimised and the digital euro will create a single market for digital retail payments.

Tokenised central bank money: powering an integrated European market for digital assets

Let me now turn to wholesale payments.

Besides seeking to offer central bank money to settle DLT-based digital asset transactions, we aim to fundamentally upgrade the infrastructure of our capital markets. If we want a future-proof savings and investments union, and if we want Europe to remain competitive, then we must collectively modernise the way financial assets are issued, traded, settled and serviced.

Europe needs to develop a market for digital assets that is based on European infrastructure, euro-denominated settlement assets and EU-wide regulation. This will also protect our strategic autonomy, monetary sovereignty and financial stability.

Safely unleashing the innovation potential of tokenisation

A key promise of DLT and tokenisation is to bring the full lifecycle of a financial transaction – issuance, trading, settlement and custody – to a single digital environment. By design, this can reduce reconciliation processes, shorten settlement chains and lower operational risk. It can also enable atomic delivery-versus-payment and support trading and settlement on a 24/7 basis, 365 days a year, rather than being constrained by the opening hours of legacy systems.^[14] Furthermore, smart contracts can automate corporate actions and cash flows that today require multiple intermediaries and manual checks.

This explains the significant interest for this technology in the European market. A large share of EU banks are experimenting with DLT applications, while a significant portion have already begun deploying them.^[15]

But a key risk is fragmentation. If tokenised payments and finance rest on fragmented pools of private settlement assets, liquidity can splinter and assets cannot be traded across platforms. Market participants may need to hold multiple stablecoins just to pay different counterparties. And in stress situations, the promise of one-to-one convertibility may be tested precisely when it matters most.

Central bank money, by contrast, is not constrained by the business model limits of private tokens. If made usable on DLT platforms, it can support the system in times of stress by elastically providing the ultimate liquidity. This matters not only for safety, but for the practical ability of a tokenised market to function smoothly at high volumes.

Establishing an integrated European market for digital assets

However, structural problems cannot be fixed by technology alone.

Europe’s post-trade landscape remains fragmented. Simply look at the number of central securities depositories across the EU, which is far higher than in other major jurisdictions. In itself, this would not be a problem, provided infrastructures were seamlessly interoperable and operated under comparable rules. But Europe still has too many operational frictions, legal discrepancies and national practices that make cross-border activity costly and complex.

A recent industry study finds that post-trade fees in Europe remain materially higher than in North America, and that fee schedules are often complex and hard to compare. Fragmentation ultimately shows up in the cost of capital and the attractiveness of European markets.^[16]

Tokenisation creates a rare opportunity to design a European market for digital assets that is integrated from the outset, in other words, a digital capital markets union. We must prevent the risk of creating platforms and standards that are incompatible and recreate the market segmentation we are trying to overcome.

We need an enabling framework that reduces legal uncertainty for tokenised securities and supports EU-wide scalability. I therefore welcome the legislative proposals published last week by the European Commission.^[17] They extend, enhance and expand the DLT Pilot Regime. And, in this respect, the idea of a dedicated EU legal framework for tokenised assets – sometimes described as a “28th regime” – captures the direction of travel.

Supporting Europe’s strategic autonomy in digital finance

Another reason to provide tokenised central bank money is to ensure a digital asset ecosystem can grow in Europe without depending on non-European settlement assets. This is key to avoiding the creation of a similar dependency in wholesale payments to what we have now in retail payments.

If we do not provide a euro-anchored wholesale solution and a European infrastructure for the settlement of digital assets, Europe could find itself importing technology, standards, governance choices and ultimately strategic dependencies. Or worse: the digital assets market could simply fail to achieve scale in Europe and could end up growing elsewhere, which would weaken the international role of the euro and our strategic autonomy. In contrast, offering tokenised central bank money will help European innovation to scale up without outsourcing the monetary anchor.

So how are we implementing this strategy in practice? In July, the ECB’s Governing Council approved a dual-track approach to settle DLT-based wholesale transactions in central bank money.^[18]

Pontes: bridging today and tomorrow

The first track, also known as Project Pontes, will deliver a regular service for settling DLT transactions in central bank money as early as the third quarter of 2026.^[19]

Pontes is designed as a bridge between DLT platforms and our existing TARGET services. This bridge will enable tokenised asset transactions recorded on market DLT platforms to settle in central bank money. It will build on existing TARGET services, so it will maintain the Eurosystem’s standards for safety, resilience and efficiency, while being cost-efficient. It will combine the features of the three solutions we used in our exploratory work, which will enable delivery-versus-payment and support automation.

We aim to gradually enhance Pontes with new functionalities following its launch, for instance by offering 24/7 operation and settlement, or by enabling the market to deploy automated smart contracts directly on the Eurosystem DLT.

In a nutshell, Pontes is about ensuring that, whichever DLT market platforms develop, safe euro settlement in central bank money will be available.

Appia: the future ecosystem

The second track, Project Appia, will lay the groundwork for an integrated European digital asset ecosystem.^[20] A launch paper to explain our vision will be published in early 2026. We want to explore how a future European digital financial market could operate if central bank money, commercial bank money and assets are able to interact efficiently in a tokenised environment.

Appia will explore two approaches, with the potential to combine them if needed. First, a European shared ledger that brings together central bank money, commercial bank money and other assets on a single platform where market stakeholders provide services. Second, a European network of interoperable platforms that reduces current frictions in the market.

This is also where the public-private partnership becomes tangible. Our role is to foster trust, develop European standards and ensure that the settlement anchor remains solid. The private sector’s role is to build the services, liquidity, business models and possibly platforms that make tokenised markets valuable.

If we get this right, Europe can achieve something that is both technologically advanced and economically decisive: a tokenised market that operates at continental scale, with European rules and the euro at its core.

Cross-border payments: openness with autonomy

Finally, we must look beyond our own borders.

Too often, cross-border payments still feel like they belong to a different era. They can be slow, expensive and opaque. According to the G20 monitoring framework, the cost of sending a USD 200 remittance averages around 6.5% of the transaction value globally, while the cost of business-to-business cross-border payments averages 1.6% of the transaction value and close to one-third of cross-border retail payments took more than one business day to be settled in 2024.^[21]

Structural factors are a significant cause of these issues. Much of the world still relies on correspondent banking chains. This model is inherently complex, as it multiplies intermediaries, compliance checks and points of failure, and it can require multiple currency conversions.

Against this backdrop, our objective is to build up European capability by combining openness and improving our payment connections with partners.

Stablecoin limits

One possible trajectory is a world in which cross-border payments increasingly depend on one or a handful of global, US-dollar-backed stablecoins distributed through dominant platforms. There are three fundamental concerns with such an outcome.

The first is concentration and operational fragility. If global payments depend on a small number of issuers and technology stacks, operational incidents, governance failures or runs become systemic issues rather than firm-level problems. Stablecoins may promise frictionless transfer but they can also create vulnerabilities in payments.

The second concern is external rule-setting via infrastructure. If the main settlement asset and rails are anchored outside Europe, then Europe’s payment outcomes are shaped elsewhere. In a world where payment networks can be weaponised, this is a risk to our economic security.

And third, there are currency substitution risks if the stablecoin ecosystem remains overwhelmingly dollar-based. If these instruments achieve scale via global platforms, they can amplify digital dollarisation dynamics – especially in regions with weaker currencies, but also by shifting the unit of account and settlement conventions in digital markets. We should avoid Europe’s cross-border payments being structurally dependent on private settlement assets denominated in another currency.

Enhancing cross-border payments

Against this backdrop, the Eurosystem has explored alternative ways to enhance cross-border payments.

TIPS already acts as a hub for instant payments within the euro area.^[22] And it is open to currencies of European countries outside the euro area, with Sweden and Denmark already using TIPS as a platform to run fast payments in their own currencies, and Norway soon to join. Since October, TIPS also provides the option to make cross-currency payments between the euro area, Sweden and Denmark.

In the near future, TIPS could evolve into a global hub for instant cross-border payments by interlinking with other fast payment systems. The Eurosystem is making progress with its work to connect TIPS with India’s Unified Payments Interface – which has one of the largest instant payment transaction volumes in the world – and with Nexus Global Payments, which will connect the fast payments systems of Malaysia, the Philippines, Singapore, Thailand and India.^[23] We also announced in September that we will start exploring the interlinking of TIPS with Switzerland’s fast payments systems, and we are in discussions with other possible partners. The Eurosystem, through Banca d’Italia, is also supporting the central banks of Albania, Bosnia and Herzegovina, Kosovo, Montenegro and North Macedonia in their efforts to develop an instant, multi-currency payments system modelled on TIPS. This “TIPS clone” is due to become operational in July 2026, after which it will be technically possible to link it up with TIPS.

This strategy will facilitate cross-border payments, making them cheaper, faster and more transparent.

Interlinking can reduce the number of intermediaries, shorten transaction chains and lower costs, as it allows payment service providers to transact without routing payments through a long chain of correspondents.

However, the settlement leg of cross-border payments, by which money moves from the payer’s to the payee’s account, is also crucial. This is why we are also exploring how tokenised settlement assets could complement interlinking. We can build on the foundation of the BIS Innovation Hub’s Project Rialto, which aims to improve instant cross-border payments using central bank money settlement. Other solutions based on tokenised forms of private money can also be explored.

Looking to the future, the digital euro could also act as a connector. It is first and foremost intended for domestic use. But it is also being designed with international use in mind, based on an approach that respects the sovereignty of other countries and mitigates potential risks.^[24]

When visiting the euro area temporarily, non-euro area residents would have access to the digital euro through a European payment service provider. Merchants outside the euro area may also be allowed to accept digital euro payments from euro area residents. Moreover, users outside the euro area could be granted permanent access to the digital euro, subject to an agreement between the EU and non-EU countries, and complemented by an arrangement between the ECB and the respective central banks. Appropriate safeguards would be put in place to avoid stoking currency substitution in those countries.

Finally, like TIPS, the digital euro’s design includes multi-currency enabling features that would allow non-euro area countries to use the digital euro infrastructure to offer their own digital currencies and facilitate transactions across these currencies.

Conclusion

Let me conclude.

In a rapidly digitalising economy where new technologies are emerging, we need to ensure central bank money remains fit for purpose. This is key for innovation, integration and independence in digital payments and digital finance.

This is of particular importance in the European context. As Mario Draghi has underlined, Europe’s problem is that innovation is often blocked by fragmented markets at the scale-up stage, pushing successful firms to seek scale elsewhere. Digital payments are a case in point and we need to avoid digital finance following the same path.

This is highly relevant for Europe’s competitiveness. Digital payments and finance stand at the interface between technology and the financial system, which together explain most of the productivity gap between Europe and the United States.^[25]

In this context, our strategy is neither state-centric nor hands-off, rather it is built around three principles.

First, central bank money must remain available and usable, also in digital form, to provide stability and trust.

Second, our approach is based on public-private partnership. The Eurosystem provides settlement in central bank money and common standards, while private intermediaries compete and innovate on top of this, delivering services that are innovative and scalable.

Third, we do not decide which technology or business models should prevail. This is up to market participants. The public sector’s role is to ensure that our payment systems and our financial system remain robust in the face of technological disruption and that markets for money and assets remain fully integrated.

In retail payments, the digital euro is about ensuring that people in Europe can continue to use public money by complementing cash with its digital equivalent. This keeps pace with the shift of commerce towards digital payments. Its infrastructure, acceptance network and standards will also make it easier for European private solutions to scale up.

In wholesale payments, Pontes in the short term and Appia in the longer term will make it possible to settle digital asset transactions in central bank money. This will provide a safe basis for tokenisation to scale in Europe.

In cross-border payments, we can increase speed and reduce costs by interlinking fast payment systems and exploring innovative settlement arrangements.

The choice, ultimately, is about whether Europe wants to sit on the sidelines watching the next wave of innovative payment solutions, or be a co-architect of an innovative, integrated and resilient digital financial system that has the euro at its core.

By acting now, as part of a public-private partnership, we can play a leading role in the transformation of money and we can embrace innovation. This will support Europe’s competitiveness, resilience and sovereignty, while delivering tangible benefits for European people and businesses.

Thank you for your attention.

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Mars Receives Final Regulatory Approval and Moves to Close the Acquisition of Kellanova

McLean, Virginia, and Chicago, Illinois (December 8, 2025) – Mars, Incorporated, a family-owned, global leader in pet care, snacking and food and Kellanova (NYSE: K), a leader in global snacking, international cereal and noodles and North America frozen foods, today announced that Mars has received unconditional approval from the European Commission for its pending acquisition of Kellanova. As a result, all required regulatory approvals and clearances for the pending transaction have been obtained.

Mars and Kellanova anticipate closing the pending transaction on December 11, 2025, subject to the satisfaction or waiver of customary closing conditions. Upon close, Kellanova’s portfolio of snacking brands, which includes Pringles®, Cheez-It®, Pop-Tarts®, Rice Krispies Treats®, RXBAR® and Kellogg’s international cereal brands, will join the existing Mars Snacking portfolio, which includes beloved brands like SNICKERS®, M&M’S®, TWIX®, SKITTLES®, EXTRA® and KIND®.  

Following the close of the pending transaction, Mars expects the combined Snacking business to generate around $36 billion in annual revenues, with a portfolio that includes 9 billion-dollar brands. Mars Snacking will continue to be headquartered in Chicago, IL and will operate in more than 145 markets, serving millions of consumers. Powered by a team of more than 50,000 Associates, it will operate 80 global production facilities and more than 170 retail outlets like Hotel Chocolat and M&M’S World.  

“We are excited to have received final regulatory approval for the pending acquisition of Kellanova,” said Poul Weihrauch, CEO and Office of the President of Mars, Incorporated. “Our focus now turns to welcoming Kellanova employees to Mars and creating an even more innovative global snacking business that delivers greater choice and quality to more consumers around the world.”  

“Today marks an extraordinary milestone and the culmination of years of work for many of our Associates,” said Andrew Clarke, Global President of Mars Snacking. “We can’t wait to welcome Kellanova talent to Mars and create a shared, global snacking leader with a beloved range of brands. We’ve said all along that Mars Snacking and Kellanova will be better together, building on the strength of our respective legacies and capabilities to unlock new possibilities and drive growth.”

Steve Cahillane, Chairman, President and CEO of Kellanova, said, “This combination will bring together two purpose-driven and principles-led companies. Serving as Kellanova’s Chairman, President and CEO has been a true honor, and I’m looking forward to seeing Kellanova people and brands thrive as part of Mars Snacking.”

The parties announced on August 14, 2024, that they had entered into a definitive agreement under which Mars agreed to acquire Kellanova. The pending transaction received Kellanova shareowner approval on November 1, 2024. The pending merger received the final of all 28 required regulatory approvals and clearances on December 8, 2025. Following the completion of the pending transaction, which remains subject to customary closing conditions, Kellanova’s common stock will be delisted and will cease trading on the New York Stock Exchange.

 

About Mars, Incorporated

Mars, Incorporated is driven by the belief that the world we want tomorrow starts with how we do business today. As an approximately $55bn, family-owned business with 150,000 Associates, our diverse portfolio of leading pet care products and veterinary services serve pets all around the world and our quality snacking and food products delights millions of people every day. We produce some of the world’s best-loved brands including ROYAL CANIN®, PEDIGREE®, WHISKAS®, CESAR®, DOVE®, EXTRA®, M&M’S®, SNICKERS® and BEN’S ORIGINAL™. Our international networks of pet hospitals, including BANFIELD™, BLUEPEARL™, VCA™ and ANICURA™ deliver high quality veterinary care and ANTECH ™ offers breakthrough capabilities in pet diagnostics.

For more information about Mars, please visit www.mars.com. Join us on Facebook, Instagram, LinkedIn and YouTube.

About Kellanova

Kellanova (NYSE: K) is a leader in global snacking, international cereal and noodles, and North America frozen foods with a legacy stretching back more than 100 years. Powered by differentiated brands including Pringles®, Cheez-It®, Pop-Tarts®, Kellogg’s Rice Krispies Treats®, RXBAR®, Eggo®, MorningStar Farms®, Special K®, Coco Pops®, and more, Kellanova’s vision is to become the world’s best-performing snacks-led company, unleashing the full potential of our differentiated brands and our passionate people.  

For more detailed information about Kellanova, please visit https://www.Kellanova.com.  

Forward-Looking Statements

This communication includes statements that constitute “forward-looking statements”  within the meaning of the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended, including statements regarding the proposed acquisition (the “Merger”) of Kellanova (the “Company”) by Mars, Incorporated (“Mars”), the expected timetable for completing the Merger, the expected benefits and other effects of the Merger,  the integration of the companies, the combined business going forward and any other statements regarding the Company’s future expectations, beliefs, plans, objectives, financial conditions, assumptions or future events or performance that are not historical facts. This information may involve risks and uncertainties that could cause actual results to differ materially from such forward-looking statements. These risks and uncertainties include, but are not limited to: the timing to consummate the Merger and the risk that the Merger may not be completed at all or the occurrence of any event, change, or other circumstances that could give rise to the termination of the merger agreement, including circumstances requiring a party to pay the other party a termination fee pursuant to the merger agreement; the risk that the conditions to closing of the Merger may not be satisfied or waived; litigation relating to, or other unexpected costs resulting from, the Merger; legislative, regulatory, and economic developments; risks that the Merger disrupts the Company’s current plans and operations; the risk that certain restrictions during the pendency of the Merger may impact the Company’s ability to pursue certain business opportunities or strategic transactions;  the diversion of management’s time on transaction-related issues; continued availability of capital and financing and rating agency actions; the risk that any announcements relating to the Merger could have adverse effects on the market price of the Company’s common stock, credit ratings or operating results; the risk that the proposed transaction and its announcement could have an adverse effect on the ability to retain and hire key personnel, to retain customers and to maintain relationships with business partners, suppliers and customers; the impact of macroeconomic conditions; other business disruptions; and consumers’ and other stakeholders’ perceptions of the Company’s brands. The Company can give no assurance that the conditions to the Merger will be satisfied, or that it will close within the anticipated time period.  

All statements, other than statements of historical fact, should be considered forward-looking statements made in good faith by the Company, as applicable, and are intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. When used in this communication, or any other documents, words such as “anticipate,” “believe,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “objective,” “plan,” “project,” “seek,” “strategy,” “target,” “will” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on the beliefs and assumptions of management at the time that these statements were prepared and are inherently uncertain. Such forward-looking statements are subject to risks and uncertainties that could cause the Company’s actual results to differ materially from those expressed or implied in the forward-looking statements. These risks and uncertainties, as well as other risks and uncertainties that could cause the actual results to differ materially from those expressed in the forward-looking statements, are described in greater detail under the heading “Item 1A. Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 28, 2024 filed with the United States Securities and Exchange Commission (the “SEC”) and in any other SEC filings made by the Company. The Company cautions that these risks and factors are not exclusive. Management cautions against putting undue reliance on forward-looking statements or projecting any future results based on such statements or present or prior earnings levels. Forward-looking statements speak only as of the date of this communication or as of any earlier date when made or deemed to have been made, and, except as required by applicable law, no person is undertaking any obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made.

Contacts  
Mars
Media:
Denise Young
Mars, Incorporated
denise.young@effem.com
Mars

Christi O’Brien
Mars, Incorporated
christi.obrien@effem.com

Kellanova  
Media:
Kellanova Media Hotline 
Media.Hotline@kellanova.com 

Investors 
John Renwick, CFA 
269-961-9050 

Brunswick Group  
Jayne Rosefield / Monica Gupta  
jrosefield@brunswickgroup.com / mgupta@brunswickgroup.com 

Introduction

Colorectal cancer (CRC) is one of the most common and lethal malignancies worldwide, particularly in developing countries. According to GLOBOCAN 2022, more than 1.93 million new CRC cases were diagnosed and approximately 904,000 deaths were recorded.¹ With the increasing implementation of colorectal cancer screening programs, a greater number of lesions are now being detected at an early stage, including malignant colorectal polyps.²

A malignant colorectal polyp is defined as a polypoid lesion in which cancer cells invade the submucosa but do not extend into the muscularis propria, corresponding to pathological stage pT1.³ The detection of such lesions raises the need to balance two treatment strategies: endoscopic polypectomy versus segmental colectomy.⁴ This growing number of early-stage diagnoses highlights the urgent need for accurate assessment of prognostic factors to guide optimal treatment decisions. Although malignant polyps represent an early stage of colorectal cancer, previous studies have reported that the rate of lymph node metastasis ranges from 5.6% to 15.2% of cases are associated with lymph node metastasis, underscoring the critical role of prognostic evaluation in determining the risk of recurrence and the need for definitive surgical management.^5–9 Several clinicopathological factors have been reported to be associated with lymph node metastasis in pT1 colorectal cancer, including tumor differentiation, lymphovascular invasion, depth of submucosal invasion, tumor budding, and tumor location.^10,11

In the context of early-stage disease, tumor budding (TB)—defined as the presence of single cancer cells or small clusters of fewer than five cells at the invasive front—has been recognized as a significant independent prognostic factor.¹² Several studies have demonstrated that in pT1 colorectal cancer, high-grade TB (≥5 buds per 0.785 mm², corresponding to grade 2 or higher according to the International Tumor Budding Consensus Conference (ITBCC) criteria) is strongly associated with lymph node metastasis.^8,12,13 Biologically, this phenomenon is closely linked to the epithelial–mesenchymal transition (EMT), a process that enables cancer cells to detach from the primary tumor and invade the surrounding stroma.^14,15 Accordingly, international guidelines, including those from CAP and NCCN, have recommended the reporting of TB in pathology assessments of pT1 colorectal cancer to support prognostication and treatment decision-making.^16,17

In routine practice, the assessment of TB on hematoxylin–eosin (H&E) slides is challenging. Tumor buds are often very small, easily mistaken for stromal elements, or obscured by inflammatory infiltrates and disrupted glandular fragments at the invasive front, leading to underestimation. Moreover, interobserver agreement in evaluating TB on H&E is generally only moderate to low.^18–20 To address these limitations, several authors have proposed the use of immunohistochemistry with pan-cytokeratin (Pan-CK), which highlights isolated tumor cells and increases sensitivity in TB detection.^21–23 Data from both research and clinical practice have shown that Pan-CK can reveal three- to four-fold more tumor buds compared with H&E,⁷ while also significantly improving reproducibility (with ICC increasing from moderate on H&E to high on Pan-CK).^18,20,24,25 Although Pan-CK offers clear advantages in early-stage CRC and has been recommended by some authors for broader application, its routine use in all cases is not feasible, particularly in resource-limited settings, due to constraints of cost, time, and technical capacity. This raises an important question as to which factors determine the necessity of Pan-CK staining in order for TB upgrading to carry prognostic significance. Based on this rationale, the present study was designed to clarify the role of Pan-CK in evaluating TB in malignant colorectal polyps (pT1) and to identify independent predictors of TB upgrading after Pan-CK staining. We anticipate that our findings will provide scientific evidence to support selective use of Pan-CK in routine practice. This selective approach is particularly relevant for low-resource settings, thereby contributing to global oncology equity.

Materials and Methods

Patient Selection and Data Collection

This retrospective study included 265 patients who were initially diagnosed with colorectal adenocarcinoma at the pT1 stage between January 2015 and June 2024 at the University Medical Center Ho Chi Minh City, Vietnam. After applying inclusion and exclusion criteria, 104 patients were eligible and included in the final analysis (Figure 1). Demographic characteristics (age, sex), clinical and endoscopic findings (tumor site and number of polyps), and laboratory data (serum CEA, lipid profile, total protein, albumin) were retrieved from electronic medical records.

Figure 1 Flow diagram of patient selection.

Inclusion criteria were: (1) histopathological confirmation of invasive adenocarcinoma confined to the submucosa (pT1 stage), (2) availability of adequate H&E-stained slides for TB assessment, and (3) complete and clearly documented clinical and pathological records. Exclusion criteria were: (1) history or synchronous of another primary malignancy, (2) prior chemotherapy, and (3) technically inadequate specimens (eg, unreadable H&E slides or severely damaged paraffin blocks).

Pathological Assessment

Histopathological variables assessed on H&E slides included histological subtype, tumor grade, depth of submucosal invasion, distance to resection margin, precursor lesion, Haggitt/Kikuchi classification, lymphovascular invasion, perineural invasion, tumor necrosis, tumor-infiltrating lymphocytes (TILs), and nodal status (for surgical specimens). Depth of submucosal invasion was assessed according to standardized criteria. Pedunculated malignant polyps were evaluated using the Haggitt classification (levels 1–4), whereas sessile lesions were assessed using the Kikuchi classification (SM1–SM3). In addition, invasion <1000 µm from the muscularis mucosae was defined as superficial and ≥1000 µm as deep. TB was initially evaluated on H&E slides according to the ITBCC 2016 criteria,¹² and the counts were recorded as baseline values. After Pan-CK immunostaining, the same invasive front was re-examined to identify the corresponding hotspot (0.785 mm² at ×20 objective). Pan-CK staining was used to confirm the epithelial nature of buds and reveal additional discrete clusters obscured by stromal or inflammatory components. The interpretation of budding morphology was based primarily on H&E features, with Pan-CK serving as a complementary tool to enhance TB detection. TB was classified as Bd1 (0–4 buds), Bd2 (5–9 buds), or Bd3 (≥10 buds). For analytical purposes, Bd1 was categorized as “low risk”, while Bd2–3 were grouped as “high risk”. Upgrading was defined as an increase in TB grade on Pan-CK compared with H&E. TB evaluation was independently performed by two pathologists who were blinded to clinical and outcome information. In cases of disagreement, the slides were jointly reviewed at a multi-headed microscope to reach a consensus. This consensus-based evaluation was intended to enhance reproducibility and ensure methodological rigor.

Immunohistochemistry Staining

For each case, serial sections were cut from formalin-fixed paraffin-embedded blocks and immunostained for cytokeratin using the Pan-CK antibody (clone AE1/AE3, Ventana, Roche Diagnostics, USA) on a fully automated BenchMark XT platform. The protocol included deparaffinization with EZ Prep solution, antigen retrieval using Cell Conditioning 1 buffer (CC1, pH 8.5, 95°C, 30 minutes), and visualization via the OptiView DAB IHC Detection Kit. Positive staining highlighted epithelial tumor cells, including isolated cells and small clusters, which were then evaluated for tumor budding (TB) according to the ITBCC 2016 criteria as described above. TB evaluation on Pan-CK–stained slides was performed by two pathologists using the same scoring approach as for H&E slides.

Statistical Analysis

All statistical analyses were conducted using Stata version 17 (StataCorp, College Station, TX, USA). Continuous variables were summarized as means ± standard deviations or medians with interquartile ranges, depending on data distribution, while categorical variables were presented as counts and percentages. Group comparisons were performed using Student’s t-test, chi-square test, or Fisher’s exact test, as appropriate. The correlation between TB counts on H&E and Pan-CK slides was assessed using Spearman’s rank correlation coefficient. To evaluate factors associated with TB upgrading, logistic regression models were applied. Multivariable logistic regression was performed, including the three variables that showed the lowest p-values in univariate analysis, given the limited number of upgrading events. A two-sided p-value < 0.05 was considered statistically significant.

Results

A total of 104 malignant colorectal polyps at the pT1 stage were included, comprising 58 males and 46 females, with a mean age of 63.88 ± 11.48 years. Of the 104 malignant polyps, 61 lesions (58.7%) were treated by endoscopic resection alone, 38 (36.5%) by surgical resection, and 5 (4.8%) by endoscopic resection followed by additional surgical resection. Most polyps were pedunculated (101 cases, 97.12%), with a mean size of 20.6 ± 12.4 mm. The most frequent tumor locations were the sigmoid colon (43 cases, 41.35%) and rectum (40 cases, 38.46%). Histologically, tubulovillous adenoma was the most common precursor lesion (60 cases, 57.69%), and adenocarcinoma not otherwise specified accounted for 94 cases (90.38%). Deep submucosal invasion was present in 87 (83.65%) cases, while lymphovascular invasion was identified in 2 cases (1.92%). Perineural invasion was not observed. Among 43 patients who underwent segmental resection or additional surgical resection, lymph node metastasis was identified in 2 cases (4.65%).

TB Assessment by Sequential H&E and Pan-CK

The number of TB foci was significantly higher on Pan-CK immunostained slides compared to H&E slides (median [IQR]: 1.0 [0.0–7.0] vs 0.5 [0.0–3.0]; p < 0.001). A strong positive correlation was observed between the two methods (Spearman’s r = 0.90, p < 0.001) (Figure 2). Based on H&E, the majority of cases were classified as Bd1 (86.54%), followed by Bd2 (12.50%) and Bd3 (0.96%). In contrast, Pan-CK staining increased the proportions of Bd2 (26 cases, 25.00%) and Bd3 (13 cases, 12.50%), while Bd1 decreased to 65 cases (62.50%). The overall agreement between H&E and Pan-CK across three Bd categories was only fair (κ = 0.301). When TB was dichotomized into low- vs high-risk (Bd1 vs Bd2/3), agreement slightly improved (κ = 0.411). Representative histological images illustrating TB on H&E and Pan-CK immunostaining are shown in Figure 3.

Figure 2 Distribution of tumor budding grades on H&E and Pan-CK immunostaining across study sample.

Figure 3 Representative histological images of tumor budding. (A and B) Cases without change in TB grade after Pan-CK immunostaining (A: H&E, ×200; (B) Pan-CK, ×200). (C and D) Cases showing upgrading from Bd1 on H&E to Bd2 on Pan-CK (C: H&E, ×200; (D) Pan-CK, ×200). Yellow arrows indicate tumor buds.

To investigate factors associated with TB grade upgrading, we focused on cases initially classified as Bd1 on H&E (n = 90), in which some were upgraded to Bd2 or Bd3 after Pan-CK immunostaining.

Clinicopathological Features Associated with TB Upgrading

Among the 90 cases initially classified as Bd1 on H&E, 25 (27.78%) were upgraded on Pan-CK (19 to Bd2 and 6 to Bd3). Several clinicopathological factors were associated with TB grade upgrading on Pan-CK staining (Tables 1 and 2). The presence of synchronous polyps defined as the coexistence of one or more additional polyps in the colorectal segment, was significantly associated with TB upgrading (36.73% vs 17.07%; OR = 2.82, 95% CI: 1.04–7.66; p = 0.042). Tumor grade 2 showed a borderline association with upgrading compared to grade 1 (33.33% vs 5.88%; OR = 8.00, 95% CI: 1.00–64.12; p = 0.050). Similarly, cases with a Haggitt/Kikuchi level ≥ 2 had a higher likelihood of upgrading than those with level 1 (38.64% vs 17.39%; OR = 2.99, 95% CI: 1.13–7.92; p = 0.028). In contrast, polyp morphology, tumor subtype, depth of invasion, precursor lesion, distance to resection margin, tumor-infiltrating lymphocytes, and tumor necrosis were not significantly associated with TB upgrading (p > 0.05).

Table 1 Clinical and Laboratory Features Associated with Tumor Budding Upgrading From Bd1 on H&E to Bd2/3 on Cytokeratin Staining

Table 2 Histopathological Features Associated with Tumor Budding Upgrading From Bd1 on H&E to Bd2/3 on Cytokeratin Staining

Multivariate Analysis

In the multivariable logistic regression model including the three significant histopathological variables from univariate analysis (Figure 4), the presence of synchronous polyps remained independently associated with TB grade upgrading (OR = 3.00, 95% CI: 1.03–8.76, p = 0.045). Tumor grade (OR = 6.42, 95% CI: 0.77–53.41, p = 0.085) and Haggitt/Kikuchi classification (OR = 2.49, 95% CI: 0.86–7.19, p = 0.091) showed strong trends toward association but did not reach statistical significance.

Figure 4 Multivariable logistic regression analysis of clinicopathological factors associated with tumor budding upgrading. Error bars represent 95% confidence intervals.

Discussion

TB, a histological manifestation of EMT has been recognized as an important prognostic factor in early-stage colorectal cancer, with high-grade TB closely associated with lymph node metastasis and poor outcomes.^12,14,15 In our study, we observed a strong correlation between H&E and Pan-CK in the assessment of TB (Spearman r = 0.90; p < 0.001). However, the number of TB identified on Pan-CK was significantly higher compared with H&E, with 27.8% (25/90) of cases initially classified as Bd1 on H&E being upgraded to Bd2–3 following Pan-CK staining.

Pan-CK has been consistently shown in multiple studies to substantially increase the number of TB detected compared with H&E. Yamadera et al reported a median TB count of 4 (range 0–20) on H&E versus 8 (range 0–40) on cytokeratin, with a statistically significant difference (p < 0.001).²⁵ Fisher et al likewise observed that the number of TB identified on Pan-CK was more than four times higher than on H&E when examined on parallel sections.²⁶ Similarly, Koelzer et al documented a three- to six-fold increase in TB counts on Pan-CK compared with H&E.²⁰ This discrepancy reflects the inherent limitations of H&E, in which TB recognition can be hampered by inflammatory infiltrates, desmoplastic reactions, or fragmented glands at the invasive front, resulting in subjectivity and suboptimal interobserver agreement. In this context, Pan-CK provides important added value by improving both the sensitivity and reliability of TB assessment in routine pathology practice. Our study also yielded similar findings, with Pan-CK detecting significantly more TB than H&E, further confirming its diagnostic utility. These results support the selective application of Pan-CK in challenging or borderline cases, consistent with CAP and ITBCC 2016 recommendations that emphasize TB reporting in pT1 CRC.^12,16 By integrating Pan-CK staining into diagnostic workflows when H&E assessment is equivocal, pathologists may achieve more reproducible TB scoring, thereby enhancing risk stratification and clinical decision-making.

In univariate analysis, two histopathological factors—Haggitt/Kikuchi classification, and the presence of synchronous polyps—were significantly associated with the likelihood of TB upgrading after Pan-CK staining. Tumors with moderate differentiation (grade 2) showed a borderline association with upgrading compared with well-differentiated tumors (grade 1). However, in multivariate analysis, only the presence of synchronous polyps remained independently associated with TB upgrading. This finding may be explained by the “field cancerization” hypothesis, which proposes that multiple neoplastic lesions represent a broader epithelial field that has undergone premalignant molecular alterations. Patel et al provided supporting evidence for this mechanism, demonstrating the presence of cancer stem cell (CSC)-like populations in morphologically normal colonic mucosa of patients with adenomatous polyps. Moreover, CSC markers such as CD44, CD166, and ESA were found to increase with age and were expressed at approximately twice the level in individuals with three to four polyps compared with those with only one to two.²⁷ These observations suggest that CSC-like cells are present not only within premalignant adenomatous polyps but also in histologically normal colonic mucosa, indicating a broader predisposition to CRC development. Taken together, our findings indicate that synchronous polyps may serve as a practical marker for identifying cases more likely to experience TB upgrading with Pan-CK. To our knowledge, this is the first study to report such an association, although further validation in larger, multicenter cohorts is warranted.

The findings of this study have important clinical implications, demonstrating that Pan-CK should be applied selectively rather than routinely to all pT1 colorectal polyps. The presence of synchronous polyps was identified as an independent predictor associated with TB upgrading. This observation suggests that Pan-CK staining should be considered particularly in cases with synchronous polyps, instead of being performed indiscriminately for all pT1 lesions. Such a selective approach may not only optimize resources and diagnostic workflows but also enhance the effectiveness of Pan-CK in risk stratification, thereby assisting clinicians in making more appropriate follow-up and treatment decisions, especially for patients with tumors harboring aggressive biological features that require definitive surgical intervention.

This study, however, has several limitations. First, it was a retrospective, single-center study with a relatively limited sample size, which reduces the statistical power and generalizability of the findings. Second, TB assessment was performed independently by two pathologists, followed by joint discussion to reach a consensus. While this approach may have improved accuracy through consensus-based interpretation, it limited the ability to assess interobserver variability, which is a critical factor when considering the true impact of Pan-CK in routine practice. Third, as 97.1% of malignant polyps in our cohort were pedunculated and only three were sessile, the findings of this study primarily apply to pedunculated lesions. The small number of sessile or non-pedunculated polyps precluded subgroup analysis; therefore, the generalizability of our results to non-pedunculated lesions should be interpreted with caution. Finally, due to the limited number of lymph node metastasis events in our cohort, we were unable to comprehensively evaluate the prognostic significance of TB upgrading on Pan-CK or determine an optimal cut-off value. These issues should be addressed in future prospective, multicenter studies with larger cohorts and long-term follow-up data.

Conclusion

Pan-CK immunohistochemistry substantially increases TB detection and grading in malignant colorectal polyps at the pT1 stage. Among cases initially classified as low-grade TB on H&E, nearly one-third were upgraded after Pan-CK staining. Notably, the presence of synchronous polyps was identified as the only independent predictor of TB upgrading—suggesting a biologically broader field effect and highlighting its potential role in refining risk stratification.

Therefore, Pan-CK should not be applied routinely to all pT1 lesions, but rather selectively—especially when synchronous polyps are present—to optimize diagnostic cost-effectiveness and support personalized decision-making. This targeted approach is particularly relevant in resource-constrained settings and aligns with the need for more sustainable, evidence-based diagnostic strategies in early colorectal cancer.

Data Sharing Statement

The datasets generated and/or analyzed during the current study are available from Dr. Phat Thi Hong Ho upon reasonable request.

Ethical Approval

The study protocol was approved by the Institutional Review Board of the University of Medicine and Pharmacy at Ho Chi Minh City (approval number: 2855/ĐHYD-HĐĐĐ). The study was conducted in accordance with the Declaration of Helsinki. Because this was a retrospective analysis of anonymized archival material, the requirement for informed consent was waived.

Acknowledgments

We gratefully acknowledge the Board of Directors of the University Medical Center, Ho Chi Minh City, as well as the Pathology Department, its physicians, technicians, and staffs for their support in data collection and laboratory procedures.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This research was financially supported by the Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City.

Disclosure

All authors have no conflicts of interest in the subject of this study.

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Lloyd’s Register (LR) has exchanged contracts for the sale of 70 Fenchurch Street, EC3, to Henderson Park, the international real estate investment manager.

The transaction follows the organisation’s relocation to its newly refurbished headquarters at 71 Fenchurch Street, London, now officially renamed the Lloyd’s Register Building.  

70 Fenchurch Street, commissioned by LR and completed in 2000, was designed by Rogers Stirk Harbour + Partners (RSHP). The building has won multiple architectural awards and served as LR’s global headquarters for more than two decades.

LR has now consolidated its London workforce into the adjacent Grade II* listed building at 71 Fenchurch Street, originally opened in 1901 and recently modernised to support hybrid working and collaboration. The restoration preserves the historic character of the site while creating a more efficient, digitally enabled workspace for LR and Lloyd’s Register Foundation.

Nick Brown, Chief Executive Officer of Lloyd’s Register, said: “The sale of 70 Fenchurch Street and our move into the refurbished Lloyd’s Register Building mark an important step in aligning our estate with the needs of a modern, global organisation. This enables us to focus investment on our people, our digital capabilities and the services that support our clients across the maritime industry.”

Henderson Park and YardNine, a central London’s office developer, plan to reposition 70 Fenchurch Street as prime, Grade A workspace. RSHP and Arup, both involved in the original development, have been appointed to advise on the refurbishment.

LR was advised on the sale by CBRE and Herbert Smith Freehills Kramer.

The ongoing pricing standoff, which began two months ago between BHP and China’s state-backed CMRG (China Minerals Resources Group), has added to uncertainty in the iron ore market. The standoff is part of China’s strategic push to exert greater influence over iron ore pricing and to increase the use of the yuan in contract settlements, reducing reliance on the US dollar.

CMRG was created by Beijing three years ago to shift leverage from major iron ore producers toward China, the world’s largest iron ore buyer.

Beijing has recently expanded its embargo on some BHP cargoes, ordering steel mills and traders to stop buying “jingbao fines”, a low-grade of iron ore that represents a small part of the miner’s exports to China. The ban follows an earlier halt on BHP’s “jimblebar fines”, a Pilbara iron ore grade and one of BHP’s most popular export types.

While the dispute is likely a negotiating tactic rather than a structural break, it heightens near-term volatility by disrupting trade flows and undermining confidence in China’s procurement approach. If unresolved, the impasse could drive a rerouting of some trade flows and force BHP to discount cargoes into alternative markets. For now, BHP has kept its full-year 2026 production guidance unchanged at 258-269 million tonnes.

We entered 2025 with a relatively bearish view of the commodities complex, while expecting gold to be the standout. And that was a pretty good call, especially when you look at oil and European natural gas. The oil market has been largely unfazed by geopolitical events and sanction uncertainty, which has seen it trade lower.

A number of agri commodities have also come under pressure, including cocoa, sugar, wheat and corn, on the back of more comfortable supply conditions. That said, wheat and corn have clawed their way back from the lows seen this year, with trade tensions easing between the US and China.

Base metal markets have performed well. While tariffs had been a downward concern, this uncertainty was more than offset by distortions seen in trade flows, with the market concerned about how trade policy will evolve. This has been particularly apparent in the copper market. The broad weakness in the US dollar would have provided further support to the metals complex.

Of course, precious metals have been the standout, with gold repeatedly hitting record highs throughout the year. Uncertainty over trade policy also led to distortions in the gold market. While heightened geopolitical risks, falling real yields, and a weaker USD all proved supportive of gold investment demand, central banks continue to make strong purchases, a trend that has been clear since the freezing of Russian assets following the Russia/Ukraine war.

For 2026, we remain bearish towards energy markets, with the global oil market set to be in large surplus, following OPEC+ rapidly ramping up output as it shifts policy, while demand growth remains modest. There is plenty of uncertainty about Russian oil supply following US sanctions, but as we move through 2026, markets will get a clearer picture of the full impact. For now, we believe the impact will be limited in the medium to long term. However, there is potential for greater volatility, given that OPEC’s spare production capacity has shrunk as the group has increased output.

While there are some short-term upside risks for the European gas market, it’s set to become better supplied, despite the region’s plans to phase out Russian gas and LNG. The start-up of LNG export capacity, particularly from the US, will leave global LNG markets and the European gas market increasingly more comfortable. However, the ramp-up of US LNG exports risks leaving the US gas market tighter.

Developments related to Russia-Ukraine peace talks will also be important to watch in 2026, with any progress towards ending the war likely to put further pressure on energy markets.

Most base metals are likely to remain well supported next year. Uncertainty over US refined copper tariffs will likely continue to see strong refined copper flows to the US, tightening up the ex-US market. And this coincides with a persistently tight copper concentrate market. For aluminium, the market is focused on China approaching its production cap, along with several producers elsewhere considering closures due to high power prices. We believe the aluminium market will be tight in 2026. For nickel, we expect little change amid persistent surpluses, keeping prices under pressure. We expect iron ore to trade lower with Chinese demand still a concern and supply growing, helped by the start of the 120mtpa Simandou mine.

We expect gold prices to remain strong and yet reach new heights. With the Fed set to cut rates and the USD likely to remain under pressure, this should be constructive for investment demand, while central banks are likely to continue adding to their reserves.

While agri commodities have seen some downward pressure this year due to strong supply and trade tensions, we believe the corn, wheat, and soybean markets are set to tighten next season, suggesting the potential for some upside in prices. However, much will depend on US trade policy with China, while for soybeans, US biofuel policy is also important.

The sugar market is set for a large surplus, driven by another strong crop from CS Brazil, while India is poised for a large recovery in output. This should keep sugar prices under pressure. The cocoa market is set for another surplus in 2025/26, suggesting prices are likely to continue trending lower from elevated levels. Finally, we also expect some moderation in the coffee market, with Brazil set to see a strong 2026/27 crop, but there are risks to this view.