Molecular genetics and endometrial cancer

Abstract

Endometrial cancer is a common gynaecological malignancy in the industrialised world. Unopposed stimulation of the endometrium by oestrogens is the classic aetiological factor associated with the development of this malignancy. However, not all are associated with oestrogen exposure and two different clinicopathological types can be distinguished: the oestrogen-related of endometrioid type (type I) and the non-oestrogen-related of non-endometrioid type (mainly papillary serous or clear cell carcinomas) (type II). Recent advances in the knowledge on the molecular genetics of endometrial cancer have shown that the molecular changes involved in its the development differ in oestrogen-dependent type I and non-oestrogen-dependent type II. Type I carcinomas frequently show mutations of DNA-mismatch repair genes (MLH1, MSH2, MSH6), PTEN, k-ras and beta-catenin genes whereas type II malignancies are characterised by aneuploidy, p53 mutations and her2/neu amplification. This article reviews the latest findings concerning common gene mutations involved in the development and progression of endometrial cancer.