Genetic markers of endometrial hyperplasia: from pathogenesis to personalization of therapy

Endometrial hyperplasia, especially in perimenopause, is a significant clinical problem in gynecology due to the high risk of malignancy to endometrial cancer, which is determined by a complex interaction of genetic disorders and hormonal imbalance. It is believed that some genetic markers (ESR1, C-MYC, PIK3CA, PTENP1, MTHFR, EGFR) affect the pathogenesis of endometrial hyperplasia by disrupting the regulation of proliferation, apoptosis, and DNA methylation. Polymorphisms of the ESR1 gene increase the density of estrogen receptors, enhancing the proliferative response of the endometrium. Overexpression of C-MYC correlates with progression to atypical forms, but it is also noted during physiological regeneration. PIK3CA mutations lead to constitutive activation of the PI3K/AKT/mTOR pathway, associated with resistance to therapy. Loss of function of the PTENP1 pseudogene disrupts the regulation of the tumor suppressor PTEN, contributing to uncontrolled growth. The MTHFR polymorphism disrupts DNA methylation, increasing sensitivity to epigenetic disorders. EGFR overexpression enhances proliferation through the MAPK/ERK pathway, especially against the background of obesity. The clinical significance of these markers often depends on background conditions, and their role remains ambiguous due to population differences and methodological heterogeneity of research. A promising direction in the treatment of this pathology is the development of integrative prognostic models combining genetic testing with clinical parameters for risk stratification and early prevention of endometrial cancer.