BIOMARKER EXPRESSION IN PROSTATIC INTRAEPITHELIAL NEOPLASIA

Objective: This study was conducted to gain a better understanding of the underlying cellular events involved in the development of prostati c intraepithelial neoplasia (PIN) and to clarify the relationship of P IN to invasive prostatic adenocarcinoma (PCa). Method: This article re views previous studies from our laboratory and others of biomarker exp ression in PIN and PCa. Results: The development of PIN is characteriz ed by increased expression of several biomarkers which may influence t he proliferative potential of the dysplastic cells. Increased expressi on of the growth factor receptors P185(erbB-2), p180(erbB-3), as well as the product of the c-met proto-oncogene is frequently detected in t he dysplastic luminal cells as well as malignant cells of the prostate . Likewise, the expression of the nm-23H1 gene product is strongly exp ressed in dysplastic and malignant cells. Increased proliferative pote ntial of the dysplastic cells is directly reflected by increased expre ssion of PCNA. In contrast to the enhanced expression of the biomarker s associated with proliferation, decreased expression of prostate-spec ific antigen (PSA), prostatic acid phosphatase (PAP) and Leu 7 by dysp lastic luminal cells is indicative of an impairment of the process of cellular differentiation. Aberrant glycosylation as well as the inappr opriate expression of glycosylated tumor antigens is demonstrated by e nhanced binding of the lectin Ulex europaeus and increased expression of tumor-associated glycoprotein 72 (TAG-72) and the Lewis Y antigen i n dysplastic and malignant cells. Finally, enhanced expression of prot eolytic enzymes such as cathepsin D and the 72-kD form of collagenase IV by dysplastic cells may represent an integral event in the developm ent of invasive PCa. Conclusion: The studies described in this review clearly demonstrate phenotypic similarities of PIN to invasive PCa and furthermore support the concept that PIN represents a preinvasive les ion.