LOSS OF EXPRESSION AND LOSS OF HETEROZYGOSITY IN THE DCC GENE IN NEOPLASMS OF THE HUMAN FEMALE REPRODUCTIVE-TRACT

In order to identify the possible role of the DCC gene in neoplasms of the human female reproductive tract, messenger RNA. expression of the DCC gene was examined by reverse transcriptase-polymerase chain react ion, and expression of the DCC gene product was detected immunohistoch emically. While histologically normal endometrium, cervical epithelium and ovary expressed detectable mRNA of the DCC gene, three of eight ( 37%) endometrial carcinomas, one of two (50%) cervical carcinomas and 9 of 22 (41%) ovarian malignant tumours had significantly reduced or n egligible DCC expression, and another endometrial carcinoma and two ot her ovarian tumors underexpressed DCC when compared with histologicall y normal endometrial or ovarian tissues. Impaired DCC mRNA expression was detected more frequently in grade 3 ovarian epithelial rumours tha n in grade 1 tumours (P = 0.002). Loss of expression of the DCC gene p roduct detected by immunohistochemistry significantly correlated with the loss of mRNA expression in ovarian carcinomas (P = 0.01 by chi-squ are test) or in both endometrial and ovarian carcinomas combined (P = 0.001). Loss of heterozygosity of the DCC gene was also evaluated by r estriction fragment polymorphism analysis of the polymerase chain reac tion-amplified DNA fragment. Loss of heterozygosity of the DCC gene wa s detected in one of seven (14%) informative cases of endometrial carc inomas, 1 of 11 (9%) informative cases of cervical carcinomas and two of six (33%) informative cases of ovarian tumours. These results demon strate that inactivation of the DCC gene, especially by the loss of ex pression, plays a significant role in the aetiology of neoplasms of th e human reproductive tract.