[Molecular carcinogenesis of ovarian carcinoma].

Correlating histological phenotype and molecular pathology epithelial ovarian tumours can be classified into a number of subgroups. High grade serous and endometrioid carcinomas are characterized by chromosomal instability which is due to functional loss of BRCA1/2 and TP53 mutations. The pattern of molecular aberrations of carcinosarcomas (Malignant müllerian mixed tumours) is similar to high grade serous carcinomas. In contrast serous borderline tumours and low grade serous carcinomas only rarely harbour complex genetic alterations. In most of these tumours the RAS-RAF signalling cascade is activated either by KRAS or by BRAF point mutation. Low grade endometrioid ovarian carcinomas contain the same molecular alterations as endometrioid carcinomas of the endometrium, in particular beta-catenin and PTEN mutations. Thus, on the molecular level they differ significantly from high grade endometrioid carcinomas of the ovary. Mucinous adenomas, borderline tumours and carcinomas are all characterized by KRAS mutations. Regarding the putative pathways of tumorigenesis a borderline--carcinoma sequence is likely for mucinous tumours and low grade serous carcinomas of the ovary. Low grade endometrioid carcinomas may originate from ovarian endometriosis. High grade endometrioid and serous carcinomas as well as carcinosarcoma putatively develop directly (de novo) from the ovarian surface epithelium or inclusion cysts.