Endometrial Cancer Signaling

Endometrial cancers are most commonly identified as adenocarcinomas. They fall into two clinicopathologic subtypes: Type I (endometrioid and mucinous carcinomas) is related to hyperestrogenism by association with endometrial hyperplasia, frequent expression of estrogen and progesterone receptors and younger age. Type II (serous and clear cell carcinomas) is unrelated to estrogen, associated with atrophic endometrium, frequent lack of estrogen and progesterone receptors and older age.Molecular/genetic changes differ between Type I and Type II carcinomas. Genetic alterations in Type I carcinomas include mutations to tumor suppressor genes PTEN and p52, microsatellite instability and mutations to oncogenes K-Ras and β-catenin. PTEN/K-Ras mutations and microsatellite instability are considered early events, occurring in a subset of atypical endometrial hyperplasias whereas p53 mutation is a later event. Type II carcinomas are most frequently caused by mutations to the p53 gene followed by amplification of the her2/neu gene.