The multicenter study analyzed nearly 2,000 digitized tissue slides from colon cancer patients across seven independent cohorts in Europe and the US. The samples included both whole-slide images of tissue samples and clinical, demographic, and lifestyle data. The researchers developed a novel "multi-target transformer model" to predict a wide range of genetic alterations directly from routinely stained histological colon cancer tissue sections. Previous studies were typically limited to predicting single genetic alterations and did not account for co-occurring mutations or shared morphological patterns.
"Earlier deep learning models and analyses of the underlying tissue alterations have generally focused on only a single mutation at a time. Our new model, however, can identify many biomarkers simultaneously, including some not yet considered clinically relevant. We were able to demonstrate this in several independent cohorts. We also observed that many mutations occur more frequently in microsatellite-instable tumors (MSI)," explains Marco Gustav, M.Sc., first author of the study and researcher at EKFZ for Digital Health at TU Dresden . Certain types of colorectal cancer can be classified based on microsatellite instability (MSI). Microsatellites are short, repetitive DNA sequences spread throughout the genome. In cancer, MSI can occur when these sequences become unstable due to defects in the DNA repair system. MSI is an important biomarker for identifying patients who may benefit from immunotherapy. "This suggests that different mutations collectively contribute to changes in tissue morphology. The model recognizes shared visual patterns, rather than independently identifying individual genetic alterations," he adds.
The researchers demonstrated that their model matched and partly exceeded established single-target models in predicting numerous biomarkers, such as BRAF or RNF43 mutations, and microsatellite instability (MSI) directly from pathology slides. The pathological expertise required to assess tissue changes from histological slides was provided by experienced medical specialists. Dr. Nic Reitsam from the University Hospital Augsburg played a key role in the study.
Highlighting the study's significance, Jakob N. Kather, Professor of Clinical Artificial Intelligence at the EKFZ for Digital Health at TU Dresden and senior oncologist at the NCT/UCC of the University Hospital Carl Gustav Carus Dresden, says: "Our research shows that AI models can significantly accelerate diagnostic workflows. At the same time, these methods provide new insights into the relationship between molecular and morphological changes in colorectal cancer. In the future, this technology could be used as an effective pre-screening tool to help clinicians select patients for further molecular testing and guide personalized treatment decisions."
The research team now plans to extend this approach to other types of cancer as well.
The study was conducted through interdisciplinary collaboration among numerous scientists at leading research institutions in Europe and the United States. In addition to TUD and Dresden University Hospital, partners included the Medical Faculty of the University of Augsburg, the National Center for Tumor Diseases (NCT) in Heidelberg, the Fred Hutchinson Cancer Center in Seattle (USA), the Medical University of Vienna (Austria), and the Mayo Clinic (USA).
Publication:
Marco Gustav, Marko van Treeck, Nic G. Reitsam, Zunamys I. Carrero, Chiara M. L. Loeffler, Asier Rabasco Meneghetti, Bruno Märkl, Lisa A. Boardman, Amy J. French, Ellen L. Goode, Andrea Gsur, Stefanie Brezina, Marc J. Gunter, Neil Murphy, Pia Hönscheid, Christian Sperling, Sebastian Foersch, Robert Steinfelder, Tabitha Harrison, Ulrike Peters, Amanda Phipps, Jakob Nikolas Kather: Assessing Genotype-Phenotype Correlations with Deep Learning in Colorectal Cancer: A Multi-Centric Study; The Lancet Digital Health, 2025.
Link: https://www.thelancet.com/journals/landig/article/PIIS2589-7500(25)00073-1/fulltext
Else Kröner Fresenius Center (EKFZ) for Digital Health
The EKFZ for Digital Health at TU Dresden and University Hospital Carl Gustav Carus Dresden was established in September 2019. It receives funding of around 40 million euros from the Else Kröner Fresenius Foundation for a period of ten years. The center focuses its research activities on innovative, medical and digital technologies at the direct interface with patients. The aim here is to fully exploit the potential of digitalization in medicine to significantly and sustainably improve healthcare, medical research and clinical practice.
