Molecular biology of prostatic intraepithelial neoplasia.

High-grade PIN is the most likely precursor of prostatic adenocarcinoma, 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 associated with progressive abnormalities of phenotype and genotype intermediate between normal prostatic epithelium and cancer, indicating impairment 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, differentiation markers, stromal markers, growth factors and associated receptors, oncogenes, tumor suppressor genes, and chromosomes. Abnormalities in expression of most biomarkers are amplified in the progression from high-grade PIN to localized cancer, metastatic cancer, and hormone-refractory cancer. Oncogenesis of prostatic carcinoma probably occurs through the selection of several genetic changes, each modifying the expression or function of genes controlling cell growth and differentiation. Further studies are needed to evaluate the function and prognostic value of oncogene expression in the normal, preneoplastic, and neoplastic prostate.