EXPRESSION OF ANDROGEN RECEPTOR AND GROWTH-FACTORS IN PREMALIGNANT LESIONS OF THE PROSTATE

Analysis of growth factors and receptors in putative premalignant lesi ons of prostatic adenocarcinoma should aid our understanding of their growth pathways, Sixty prostatic TURF (transurethral resection of the prostate) specimens exhibiting atypical adenomatous hyperplasia (AAH) and/or prostatic intraepithelial neoplasia (PIN) lesions mere assayed by immunohistochemistry for androgen receptor (AR), epidermal growth f actor receptor (EGFR), c-erbB-2, transforming growth factor-alpha (TGF -a), vascular endothelial growth factor (VEGF), fibroblast growth fact or-2 (FGF-2), MIB-1, E-cadherin, and high molecular weight keratin. Ex pression of these factors in the lesions was compared with that in the co-existing benign prostatic hyperplasia (BPH) or prostatic adenocarc inoma, Strong AR nuclear staining was observed in the luminal cells, b ut not the basal cells, of BPH and PIN lesions and in all the carcinom as examined, A similar growth factor and receptor profile mas demonstr ated in the secretory epithelium of high-grade PIN and carcinoma with a tendency to higher expression of membranous EGFR and c-erbB-2 and cy toplasmic TGF-a, and lower levels of FGF-2 than in low-grade PIN or BP H glands, Also, increased rates of proliferation, as estimated by MIB- 1 stained cells, mere observed in high-grade PIN in comparison with lo w-grade PIN and BPH and mere not confined to the basal layer, AAH lesi ons resembled neither BPH nor carcinoma, Proliferation was virtually a bsent (MIB-1 expression); both AR and E-cadherin expression was signif icantly reduced; and, with the exception of FGF-2, all the other growt h factors and receptors studied mere absent, The results presented wou ld support a premalignant role for high-grade PIN, whilst AAH would ap pear to represent a quiescent phenotype unlikely to progress to neopla sia, (C) 1998 John Wiley & Sons, Ltd.