THE LOCALIZATION OF TRANSFORMING-GROWTH-FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR RECEPTOR IN STROMAL AND EPITHELIAL COMPARTMENTS OF DEVELOPING HUMAN PROSTATE AND HYPERPLASTIC, DYSPLASTIC, AND CARCINOMATOUS LESIONS

To gain insight into autocrine/paracrine mechanisms that may influence normal and abnormal growth of the human prostate, we studied the immu nohistochemical localization of transforming growth factor alpha (TGF- alpha) and epidermal growth factor receptor (EGFr) in fetal, neonatal, prepubertal, and young adult glands. Results were compared with findi ngs in specimens of benign prostatic hyperplasia (BPH), dysplasia (pro static intraepithelial neoplasia-PIN), and carcinoma. EGFr was strongl y and exclusively expressed in fetal basal cells, whereas TGF-alpha wa s localized in these and secretory cells as well as in differentiating smooth muscle cells. In neonatal and prepubertal glands, EGFr continu ed to be found only in basal cells, whereas TGF-cu was now present in smooth muscle and infrequently in secretory cells. In the normal adult prostate, the receptor was strictly localized in basal cells and in t he lateral plasma membranes of secretory cells, whereas its ligand was exclusively expressed in smooth muscle. This pattern persisted in PBH , but both EGFr and TGF-alpha staining appeared to be enhanced in thei r respective cellular compartments. Irrespective of grade, in dysplasi a diffuse-moderate EGFr and strong TGF-alpha staining were both presen t in a majority of secretory cells. Similarly, most cells in Gleason g rade 3 and 4 carcinomas expressed both EGFr and TGF-cl. Our finding su ggest that an unregulated paracrine mode of growth attends the develop ment of BPH, whereas malignant transformation and progression involves autocrine/paracrine mechanisms reminiscent of those found in the deve loping prostate. Copyright (C) 1998 by W.B. Saunders Company.