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Four molecular subtypes with different clinical outcomes have been identified: POLE mutation, mismatch repair deficient, p53 abnormal, and no specific molecular profile. However, determining these subtypes typically relies on expensive gene sequencing. To overcome this limitation, we propose a novel method that utilizes hematoxylin and eosin-stained whole slide images to predict endometrial cancer molecular subtypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our approach leverages a hierarchical foundation model as a backbone, fine-tuned from the UNI computational pathology foundation model, to extract tissue embedding from different scales. We have achieved promising results through extensive experimentation on the Fudan University Shanghai Cancer Center cohort (N\u2009=\u2009364). Our model demonstrates a macro-average AUROC of 0.879 (95% CI, 0.853\u20130.904) in a five-fold cross-validation. Compared to the current state-of-the-art molecular subtypes prediction for endometrial cancer, our method outperforms in terms of predictive accuracy and computational efficiency. Moreover, our method is highly reproducible, allowing for ease of implementation and widespread adoption. This study aims to address the cost and time constraints associated with traditional gene sequencing techniques. By providing a reliable and accessible alternative to gene sequencing, our method has the potential to revolutionize the field of endometrial cancer diagnosis and improve patient outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The codes and data used for generating results in this study are available at https:\/\/github.com\/HaoyuCui\/hi-UNI for GitHub and https:\/\/doi.org\/10.5281\/zenodo.14627478 for Zenodo.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf059","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T11:29:47Z","timestamp":1739273387000},"source":"Crossref","is-referenced-by-count":11,"title":["Prediction of molecular subtypes for endometrial cancer based on hierarchical foundation 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