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Nearly three fourths of women are diagnosed after the tumor has spread beyond the confines of the ovary. The overall survival for high stage invasive ovarian cancer is only 20%, underscoring the need for early identification and intervention. The incidence of ovarian cancer increases with age, and is related to a variety of influences such as nulliparity, disordered ovarian function, and family history. Familial cases account for about 5% of all ovarian tumors.
Epithelial cancers comprise approximately 75% of ovarian tumors, and are in turn subdivided into benign, borderline (low malignant potential) and frankly malignant categories. Borderline tumors have the cytologic features of malignancy, but do not invade the stroma, and up to three fourths present at an early stage, with survival approaching 100% for such cases. There are five major types of ovarian epithelial tumors, including serous, mucinous, clear cell, endometrioid, and transitional cell (Brenner tumors). The non-epithelial ovarian tumors include the germ cell tumors (teratoma, dysgerminoma, choriocarcinoma, endodermal sinus tumors), and sex-cord stromal tumors (Sertoli-Leydig cell, granulosa cell tumors), both of which have a distinct biology and molecular profile from the epithelial neoplasms.
The molecular biology of ovarian cancers has been best studied in the spectrum of epithelial tumors. p53, the most commonly implicated tumor suppressor gene in human cancers, is mutated in 40-50% of ovarian carcinomas. The incidence of p53 mutations have been found to increase from early stage to advanced stage tumors, suggesting that loss of p53 function may be associated with disease progression. Mutations in the two familial breast cancer genes BRCA1 and BRCA2 also predispose to an increased risk of ovarian cancers; 30-60% of patients carrying germline BRCA1 mutations develop ovarian cancers before the age of 70 years. Notably, somatic mutations of BRCA1 and BRCA2 are also found in sporadic ovarian cancers, underscoring the importance of these two genes in carcinogenesis. In addition to these tumor suppressor genes, several oncogenes have been implicated in ovarian tumorigenesis. These include the Her-2/neu oncogene, amplification of which, as in breast cancers, is associated with an adverse prognosis. Nearly a third of ovarian tumors demonstrate Her-2/neu amplification, and it is usually restricted to the malignant tumors. Similarly, overexpression of the epidermal growth factor receptor (EGFR) is associated with a poor prognosis, shortened survival and increased risk of progression. A small proportion of ovarian cancers demonstrate activating mutations of the K-ras oncogene, usually on codon 12, and these are more frequent in the mucinous than serous epithelial tumors. |
