THE RELATIONSHIP BETWEEN PROSTATIC INTRAEPITHELIAL NEOPLASIA AND PROSTATE-CANCER - CRITICAL ISSUES

Purpose: Prostatic intraepithelial neoplasia (PIN) is often considered to be a premalignant lesion and the main precursor of invasive carcin oma of the prostate. We evaluated the evidence for and against PIN as a premalignant lesion and determined guidelines for the clinical manag ement of PIN. Materials and Methods: Literature analysis of histopatho logical, morphometric, phenotypic and molecular genetic evidence of pr ogression and of clinical findings regarding PIN was done. Literature searches were performed on MEDLINE with relevant key words. Results: P IN, like prostate cancer, occurs most frequently in the peripheral zon e of the prostate and is usually located in close proximity to prostat e cancer. The relative PIN and prostate cancer volumes vary inversely. Prostate specific antigen in cases of PIN appears to be intermediate between prostate cancer and normal levels, although this elevation may be explained by concomitant prostate cancer or benign prostatic hyper plasia. Deoxyribonucleic acid ploidy in PIN follows the aneuploid prop ortion as in the concomitant prostate cancer. Prostate cancer and PIN show evidence of loss of putative tumor suppressor genes on chromosome 8p. The clinical relevance of PIN biopsy findings is based on the ass ociation of neoplasia and prostate cancer. High grade PIN in core biop sies without concomitant prostate cancer has a substantial risk for pr ostate cancer in subsequent biopsies (24 to 73%, up to 100% when the d igital rectal examination is suspicious) and should cause further biop sy sampling. Conclusions: There is convincing evidence that PIN is a p recursor lesion to prostate cancer, with a close association of PIN an d prostate cancer in biopsy and prostatectomy specimens. A biopsy find ing of high grade PIN necessitates further investigation in patients w ho are candidates for radical treatment for localized prostate cancer.