P53 MUTATIONS IN OVARIAN-TUMORS, DETECTED BY TEMPERATURE-GRADIENT GEL-ELECTROPHORESIS, DIRECT SEQUENCING AND IMMUNOHISTOCHEMISTRY

Samples from 94 ovarian tumors, comprising 24 cystadenomas/adenofibrom as, among them 6 benign and 18 borderline tumors, one benign Brenner t umor, 39 carcinomas, 17 sex-cord stromal tumors, 5 germ-cell tumors an d 8 metastatic or recurrent neoplasms were screened for p53 aberration s by polymerase chain reaction (PCR), temperature-gradient gel electro phoresis (TGGE), direct sequencing and immunohistochemistry. All sex-c ord stromal and germ-cell tumors showed wild-type p53, except for a he terozygous silent germ-line mutation in one androblastoma. Somatic p53 mutations were detected in only one tumor of the cystadenoma/adenofib roma 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 endometrio id and mucinous carcinomas. By direct sequencing, the mutations of 13 cases were qualified as mis-sense mutations (n = 10), or 1 to 2-bp del etions (n = 3). Only 2 cases were immunohistochemically positive in th e absence of detectable p53-gene abnormalities. The presence of p53 ab errations was significantly correlated with high grade, but not with s tage of disease. For 21 bilateral tumors and/or tumors spread to the p eritoneum, samples from both ovaries and/or ascites were analyzed. Amo ng these, 16 cases were identical as to the p53 genotype, 5 cases show ed discordant p53 states in ovary and/or in ascites DNA. We conclude t hat somatic p53 mutations are very frequent in serous papillary carcin omas, particularly in tumors of high grade, bilaterality, and peritone al spread, less frequent in other carcinoma types and extremely rare i n borderline and benign tumors of the ovary. (C) 1995 Wiley-Liss, Inc.