Genetic alterations of the WT1 gene in papillary serous carcinoma of the peritoneum

Objective. The Wilms' tumor (WT1) gene product is consistently detectable i n both normal ovarian germinal epithelium and human mesothelium, Ovarian ca rcinomas frequently exhibit alterations in WT1 function. Papillary serous c arcinoma of the peritoneum (PSCP) is believed to develop de novo from the p eritoneal lining (mesothelium) of the pelvis and abdomen. The purpose of th is study was to determine if genetic alterations of the WT1 gene are associ ated with the development of PSCP. Methods. Normal and tumor tissue specimens were retrieved from patients wit h stage III and IV PSCP (n = 38) and serous epithelial ovarian carcinoma (n = 38). Immunohistochemistry was performed using the anti-WT1 (C-19) antibo dy. Loss of heterozygosity (LOH) was performed at the WT1 locus. Clinical d ata were obtained and correlated with molecular findings. Results. Loss of normal WT1 expression was detected in 18 (51%) of 35 PSCP specimens and 18 (53%) of 34 ovarian carcinoma specimens. Six (27%) of 22 P SCP specimens and 3 (13%) of 24 ovarian carcinoma specimens had LOH at the WT1 locus (P = 0.27), Normal WT1 gene expression was maintained in 86% of t umors exhibiting LOH. Genetic alterations of the WT1 gene were not predicti ve of survival, nor were they associated with other clinical or molecular f actors. Conclusions, Genetic alterations of the WT1 gene are associated with the de velopment of PSCP, The loss of normal WT1 gene expression is a common event in both PSCP and advanced ovarian carcinoma, likely resulting from down-re gulation by other regulatory factors-not from inactivating gene mutation an d subsequent allelic loss. (C) 2000 Academic Press.