p53 mutations in ovarian tumors, detected by temperature-gradient gel electrophoresis, direct sequencing and immunohistochemistry.

Samples from 94 ovarian tumors, comprising 24 cystadenomas/adenofibromas, among them 6 benign and 18 borderline tumors, one benign Brenner tumor, 39 carcinomas, 17 sex-cord stromal tumors, 5 germ-cell tumors and 8 metastatic or recurrent neoplasms were screened for p53 aberrations by polymerase chain reaction (PCR), temperature-gradient gel electrophoresis (TGGE), direct sequencing and immunohistochemistry. All sex-cord stromal and germ-cell tumors showed wild-type p53, except for a heterozygous silent germ-line mutation in one androblastoma. Somatic p53 mutations were detected in only one tumor of the cystadenoma/adenofibroma series (4.2%), in contrast to 38.5% of the carcinomas, among them 57.1% of serous papillary carcinomas, and 12.5 to 22.2% of endometrioid and mucinous carcinomas. By direct sequencing, the mutations of 13 cases were qualified as mis-sense mutations (n = 10), or 1 to 2-bp deletions (n = 3). Only 2 cases were immunohistochemically positive in the absence of detectable p53-gene abnormalities. The presence of p53 aberrations was significantly correlated with high grade, but not with stage of disease. For 21 bilateral tumors and/or tumors spread to the peritoneum, samples from both ovaries and/or ascites were analyzed. Among these, 16 cases were identical as to the p53 genotype, 5 cases showed discordant p53 states in ovary and/or in ascites DNA. We conclude that somatic p53 mutations are very frequent in serous papillary carcinomas, particularly in tumors of high grade, bilaterality, and peritoneal spread, less frequent in other carcinoma types and extremely rare in borderline and benign tumors of the ovary.