EXPRESSION OF P160(ERBB-3) AND P185(ERBB-2) IN PROSTATIC INTRAEPITHELIAL NEOPLASIA AND PROSTATIC ADENOCARCINOMA

Background: Although prostatic adenocarcinoma is the most frequent mal ignancy among American men, little is known concerning the roles of gr owth factors, growth factor receptors, or proto-oncogene products in t he development and progression of this malignancy. Purpose: We examine d and compared the expression and cellular distribution of the erbB-3 protein (p160(erbB-3)) and the erbB-2 protein (p185(erbB-2)) in variou s stages of development and progression of prostatic adenocarcinoma. M ethods: Immunoperoxidase staining was used to determine the expression of p160(erbB-3) and p185(erbB-2) in benign prostatic epithelium, pros tatic intraepithelial neoplasia, localized adenocarcinomas (pathologic stages B and C) as well as matching primary and lymph node lesions fr om patients with stage D adenocarcinoma. In order to test antibody spe cificity, we used Western blot analysis to examine the expression of p l60(erbB-3) and p185(erbB-2) in selected prostatic adenocarcinomas. Re sults: Within benign glands, immunostaining for p160(erbB-3) or p185(e rbB-2) mag strongest in the basal cells and was typically absent or we ak in the luminal (secretory) cells. Expression of both proteins withi n luminal cells was localized to cell membranes. We examined the expre ssion of p(160erbB-3) and p185(erbB-2) in the prostatic intraepithelia l neoplastic lesions of 22 radical prostatectomy specimens. Like benig n glands, the basal cells of these neoplastic lesions typically demons trated strong to moderate immunostaining when stained with either anti body. In contrast to benign glands, moderate to strong immunostaining for p160(erbB-3) and p185(erbB-2) was frequently observed within the c ytoplasm and cell membranes of the prostatic intraepithelial neoplasti c luminal cells. p160(erbB-3) and p185(erbB-2) were detected within th e malignant cells in 28 and 29 of 29 localized adenocarcinomas, respec tively. Immunostaining with either antibody was typically moderate to strong in the malignant cells. Both proteins were expressed on the cel lular membranes as well as in the cytoplasm of malignant cells. Immuno staining for p160(erbB-3) was detected in the matching primary and met astatic lesions (lymph nodes) in 10 of 11 patients with stage D adenoc arcinoma. carcinoma. Immunostaining for p185(erbB-2) was detected in m atching primary and metastatic lesions (lymph nodes) obtained from 16 patients with stage D adenocarcinoma. Western blot analysis confirmed the specificity of the antibodies. Conclusions: These results suggest that increased expression and changes in the subcellular distribution of both p160(erbB-3) and p185(erbB-2) represent early events in the de velopment and progression of prostatic adenocarcinomas. The high expre ssion and distribution of both p160(erbB-3) and p185(erbB-2) are retai ned both in advanced-stage primary and metastatic tumors.