TCF-alpha RIA results from women with disseminated breast carcinoma were compared with those of healthy pre- and post- menopausal control women. Statistical analysis indicated a mean TGF-alpha value of 1,144 ng/g urinary creatinine for tumored urine samples (range 608 to 1,737) and 613 ng/g creatinine (range 417 to 941) for the control urine samples. Although the difference was statistically significant (p less than 0.05), because of tes overlap between groups, urinary TGF-alpha detection appears to have limited usefulness as a diagnostic marker for metastatic human adenocarcinoma of th breast; however, it does confirm that a subset of women with metastatic breast cancer do have greatly increased TCF-alpha in their urine. Additional studies indicate that the urine of women with metastatic epithelial ovarian cancer contains two-to-three fold higher levels of TGF-alpha than that subset of women with breast carcinoma. Accordingly, we are examining TGF-alpha expression by RIA, ELISA, and Western immunoblots in 1) conditioned media of 14 ovarian cell lines, 2) benign and malignant ovarian cyst fluid samples, and 3) peritoneal effusions from ovarian cancer patients. The potential autocrine regulation of growth in ovarian carcinoma is being evaluated by 1) EGF-receptor analysis to generate receptor number per cell (B max.) and dissociation constants (Kd) of the ovarian cell lines and 2) their growth inhibition by neutralizing anti-TCF alpha and anti-EGF- monoclonal antibodies. To date, TGF-alpha RIA and EGF-receptor binding studies indicate: 1) each of the 14 ovarian carcinoma lines secrete TGF-alpha ranging from 0.13 to 0.98 ng/ml in conditioned media, or 0.012 to 1.99 ng per 10 to the 8th powe cells in culture; and 2) EGF-receptors are expressed in each line.
