[Serous genital carcinoma: molecular pathogenesis and the role of tubal fimbria].

Serous carcinomas develop at various sites of the Mullerian system, in particular, the ovaries, the peritoneum, the uterus and the fallopian tubes. Currently, two distinctive molecular genetic pathways are distinguished for serous tumorigenesis: type I tumors are typically well differentiated and gradually develop from cystadenoma through borderline tumor to low grade carcinoma and are characterized by B-raf and K-ras mutations, whereas the poorly differentiated type II tumors develop from intraepithelial carcinoma and show p53 mutations. Infrequently, p53 mutations occur as a late event in the type I pathway and lead to a high grade tumor phenotype. A histologically inconspicuous possible precursor lesion of the intraepithelial carcinoma is the p53 signature that shows p53 overexpression without cell cycle deregulation. Whereas in the ovaries both pathways may occur and develop from inclusions of the surface epithelium, the fallopian tube has recently been described as an important site for the type II pathway. High grade serous carcinomas and intraepithelial carcinomas of the tubal fimbria are particularly found in patients with BRCA1/BRCA2 germ line mutations. Since an advanced tumor stage is frequent and often makes the determination of the origin impossible, the term pelvic serous carcinoma was recently proposed for high grade serous (adeno)carcinomas involving multiple sites.