Rb. Myers et al., EXPRESSION OF P160(ERBB-3) AND P185(ERBB-2) IN PROSTATIC INTRAEPITHELIAL NEOPLASIA AND PROSTATIC ADENOCARCINOMA, Journal of the National Cancer Institute, 86(15), 1994, pp. 1140-1145
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.