H&E-based MSI/MMR testing with AI in colorectal cancer: a multi-centred blinded evaluation
By
Cher Bass
Foivos Ntelemis
Julian Schmidt
Steffen Wolf
André Geraldes
Debapriya Mehrotra
Shikha Singhal
Narender Kumar
Angelica Marcia
Nicholas Bennett
Oscar Maiques
Mitchell Hyde
Bejal Mistry
Grace Rogerson
Michele Cummings
Clare Freer
Elizabeth Walsh
Manuel Salto-Tellez
Maurice Loughrey
In Hwa Um
David J. Harrison
Richard Clarkson
James Blackwood
J. Carl Barrett
Jakob Nikolas Kather
Nicolas M. Orsi
Pahini Pandya
Salim Arslan
December 15, 2025
Clinical Scorecard: AI-Enhanced H&E-Based Assessment of MSI and MMR in Colorectal Cancer: A Blinded Multi-Center Study
At a Glance
Category Detail
Condition Colorectal cancer with mismatch repair deficiency and microsatellite instability Key Mechanisms Mismatch repair deficiency leads to microsatellite instability, detectable via AI analysis of H&E-stained slides Target Population Patients with colorectal cancer undergoing MSI/MMR status assessment Care Setting Pathology laboratories and oncology diagnostic workflows in hospital and clinical settings
Key Highlights
Mismatch repair deficiency occurs in 10–20% of colorectal cancers and is critical for guiding treatment decisions. PANProfiler Colorectal (PPC) uses AI to determine MSI/MMR status directly from routine H&E-stained slides with high accuracy. Blinded multi-center validation showed PPC achieved over 93% overall agreement with standard MSI/MMR testing methods. Guideline-Based Recommendations
Diagnosis
MSI/MMR testing is recommended for all colorectal cancer patients by NICE, ESMO, ASCO, and CAP. Current standard methods include immunohistochemistry (IHC) and PCR-based MSI testing. AI-based assessment from H&E slides offers a rapid, cost-effective alternative to conventional testing. Management
MSI-H and dMMR status guide immunotherapy decisions, with high response rates to immune checkpoint inhibitors. Accurate MSI/MMR testing informs prognosis and identifies candidates for Lynch syndrome testing. Monitoring & Follow-up
Regular assessment of MSI/MMR status is important for treatment planning and monitoring therapeutic response. Risks
IHC interpretation can be subject to inter-observer variability. PCR testing may be limited by poor DNA quality from FFPE samples. Delays and costs associated with conventional testing can impact timely treatment decisions. Patient & Prescribing Data
Colorectal cancer patients undergoing MSI/MMR status evaluation
MSI-H/dMMR tumors show approximately 50% response rates to immunotherapy in metastatic CRC and up to 100% in early-stage disease.
Clinical Best Practices
Implement universal MSI/MMR testing for all colorectal cancer patients as per international guidelines. Utilize AI-based tools like PANProfiler Colorectal to enhance accessibility, reduce turnaround times, and lower costs. Interpret AI results in conjunction with clinical and pathological findings to guide treatment decisions. Ensure quality control and validation of AI tools across diverse clinical settings and populations. References
