Expression of transforming growth factor-alpha and the epidermal growth factor receptor in human prostate tissues.

Cells respond to certain soluble factors that bind to cell surface receptors possessing intrinsic tyrosine kinase activity. Overexpression of these molecules has been associated with tumor progression. Enhanced prostatic cancer cell growth in vitro has been reported in the presence of certain growth factors. To characterize the patterns of expression of the epidermal growth factor receptor (EGFr) and transforming growth factor-alpha (TGF alpha), we studied tissue from 107 prostate specimens using immunohistochemistry. We observed that epithelial cells of normal (n = 4) and benign prostatic (n = 56) tissues express EGFr but were unreactive for TGF alpha, while stroma cells in these tissues express TGF alpha but not EGFr. However, coexpression of EGFr and TGF alpha was identified in 22 of 46 prostatic adenocarcinomas studied. These results suggest that the major mode of action of EGFr/TGF alpha in normal and benign prostate is that of a paracrine or juxtacrine loop, the ligand being expressed in the stroma cells and the receptor in the epithelial cells. Since a subset of prostatic carcinomas coexpressed the ligand and the receptor in their tumor cells, it is suggested that an independent autocrine signaling mechanism may occur and grant a selective advantage for the growth of prostate cancers.