H&E-based MSI/MMR testing with AI in colorectal cancer: a multi-centred blinded evaluation

Abstract

Mismatch repair (MMR) deficiency occurs in 10–20% of colorectal cancer (CRC) cases, leading to microsatellite instability (MSI). Although MSI/MMR testing is critical for CRC management, high costs and long turnaround times limit testing rates and clinical utility, highlighting the need for more accessible, cost-effective alternatives. PANProfiler Colorectal (PPC) is an artificial intelligence (AI)-based biomarker test that determines MSI/MMR status directly from haematoxylin and eosin (H&E)-stained slides. We conducted a blinded, multi-centred validation to assess PPC’s performance against standard testing. The study included 3,576 whole slide images from 1,243 CRC patients across three United Kingdom institutions. PPC produced definitive results for 86.55% of slides, achieving an overall agreement of 93.83%, positive agreement of 92.54%, and negative agreement of 94.02%. PPC accurately determined MSI/MMR status from routine H&E slides, offering a rapid, scalable alternative to conventional diagnostic methods.

Metadata

Item Type:	Article
Authors/Creators:	Bass, C. Ntelemis, F. Schmidt, J. Wolf, S. Geraldes, A. Mehrotra, D. Singhal, S. Kumar, N. Marcia, A. Bennett, N. Maiques, O. Hyde, M. Mistry, B. Rogerson, G. Cummings, M. Freer, C. Walsh, E. Salto-Tellez, M. Loughrey, M. Um, I.H. Harrison, D.J. Clarkson, R. Blackwood, J. Barrett, J.C. Kather, J.N. Orsi, N.M. Pandya, P. Arslan, S.
Copyright, Publisher and Additional Information:	© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 24 November 2025 Published (online): 15 December 2025 Published: 15 December 2025
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds)
Date Deposited:	03 Feb 2026 15:15
Last Modified:	03 Feb 2026 15:15
Published Version:	https://www.nature.com/articles/s41746-025-02218-5
Status:	Published
Publisher:	Springer Nature
Identification Number:	10.1038/s41746-025-02218-5
Related URLs:	Author Dataset
Sustainable Development Goals:
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:237306