CLINICAL-SIGNIFICANCE OF ONCOGENES AND GROWTH-FACTORS IN OVARIAN CARCINOMAS

The expression of epidermal growth factor receptor (EGF-R), transforming growth factor alpha (TGF-alpha) and the c-myc oncogene was investigated in different specimens of gynecologic carcinomas. EGF specific binding sites were detected in about 50% of adenocarcinomas (ovarian, endometrial, breast) and in over 90% of squamous carcinomas (cervical). There is a positive correlation between the EGF-R binding assay, immunohistochemistry and the relative amounts of mRNA by Northern blotting. TGF-alpha was investigated by immunohistochemistry and Northern blotting. TGF-alpha immunoreactivity was detected exclusively in the epithelial cells of nonmalignant tissues (skin, cervix, endometrium, large bowel, lung) as well as different ovarian carcinomas. The TGF-alpha immunostaining score correlates with the TGF-alpha mRNA amounts. The c-myc expression was analyzed by Northern blotting in the specimens of ovarian carcinomas. Whereas, a positive correlation between the c-myc and TGF-alpha expression was noticed, no correlation existed between EGF-R and c-myc expression. Progressive disease (PD) of ovarian carcinomas after chemotherapy was mainly noticed in the group of EGF-R- tumors and those with high amounts of c-myc mRNA. EGF-R+ ovarian carcinomas responded significantly better to chemotherapy. However, similar survival times existed between the EGF-R+ and EGF-R- group and the survival times of patients having responded to the treatment was reduced in the EGF-R+ group. This indicates that EGF-R+ and those carcinomas expressing high amounts of c-myc constitute a more aggressive group of ovarian carcinomas.