A multistep model for ovarian tumorigenesis: the value of mutation analysis in the KRAS and BRAF genes

Epithelial ovarian tumours represent a complex group of histological subtypes and there has long been controversy over the question of a precursor lesion for these neoplasms. The application of mutation analysis of the KRAS and BRAF genes (members of the RAS-RAF-MEK-ERK-MAP kinase pathway) is consistent with the model for progression of mucinous carcinomas and a subset of serous carcinomas (the so-called low-grade serous carcinomas) through benign and borderline lesions. The relatively high incidence of BRAF and KRAS mutations in serous borderline tumours and low-grade serous carcinomas, and their extremely low incidence/absence in high-grade serous carcinomas, provide strong evidence that high-grade carcinomas do not arise through this intermediate step.