Integrating POLE Mutations and Mismatch Repair Status in Personalized Medicine for Endometrial Cancer

Endometrial cancer represents one of the most common gynecologic malignancies worldwide, with molecular profiling emerging as a transformative approach to its classification and treatment. The traditional histopathological model, based on tumor grade and morphology has evolved with the advent of genomic technologies, leading to the development of The Cancer Genome Atlas (TCGA) molecular subtypes: POLE ultra mutated, microsatellite instability-high (MSI-H) or mismatch repair-deficient (DMMR), copy-number low, and copy-number high. POLE-mutated tumors, characterized by ultrahigh mutational burden and microsatellite stability, generally have excellent prognosis, whereas MSI-H/ DMMR tumors respond favorably to immune checkpoint inhibitors. This review article was intended to underlie the importance of personal treatment of every patient because they exhibit unique molecular characteristics, leading to variations in prognosis and therapeutic response. Therefore, tailoring management to these molecular profiles is essential to achieve optimal outcomes. Integrating immunohistochemistry, PCR, and next-generation sequencing facilitates accurate molecular classification and individualized therapy. The convergence of molecular pathology and genomics represents a paradigm shift in endometrial cancer care, positioning POLE and MMR testing as cornerstone biomarkers for truly personalized medicine.