MOLECULAR-BIOLOGY OF PROSTATIC INTRAEPITHELIAL NEOPLASIA

High-grade PIN is the most likely precursor of prostatic adenocarcinom a, according to virtually all available evidence to date. The clinical importance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN has a high predictive value as a marker for adenocarcinoma. Its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. PIN is ass ociated with progressive abnormalities of phenotype and genotype inter mediate between normal prostatic epithelium and cancer, indicating imp airment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. There is progressive gain or loss of a wide variety of biomarkers, including morphometric markers, diffe rentiation markers, stromal markers, growth factors and associated rec eptors, oncogenes, tumor suppressor genes, and chromosomes. Abnormalit ies in expression of most biomarkers are amplified in the progression from high-grade PIN to localized cancer, metastatic cancer, and hormon e-refractory cancer. Oncogenesis of prostatic carcinoma probably occur s through the selection of several genetic changes, each modifying the expression or function of genes controlling cell growth and different iation. Further studies are needed to evaluate the function and progno stic value of oncogene expression in the normal, preneoplastic, and ne oplastic prostate. (C) 1996 Wiley-Liss, Inc.