Prostatic intraepithelial neoplasia: the preinvasive stage of prostate cancer. Overview of the prostate committee report.

About 200000 American men are diagnosed with prostate cancer each year, and millions more develop undiagnosed preclinical microscopic cancer. About 80% of men have microscopic prostate cancer by the age of 80, and the autopsy prevalence is remarkably similar around the world despite large differences in clinical detection. What is the origin of all of these prostate cancers? If we knew the answer to this question, then effective measures could be developed to prevent cancer and thus conquer the second leading cause of cancer death among American men and a leading cause of death for men worldwide. This question was the focus of the deliberations of the prostate consensus group at the World Health Organization meeting in Stockholm. Remarkably, our question appears to be answerable for the majority of cases of prostate cancer. High-grade prostatic intraepithelial neoplasia (PIN) is the most significant risk factor for prostate cancer in needle biopsy specimens, and is considered to be the preinvasive stage of cancer. Its role as a precursor of cancer was recently confirmed conclusively in two separate mouse models (1, 2). The microscopic finding known as PIN is characterized by cellular proliferations within pre-existing ducts and acini with cytologic changes mimicking cancer, including nuclear and nucleolar enlargement (3). PIN coexists with cancer in >85% of cases (3) but retains an intact or fragmented basal cell layer, unlike cancer, which lacks a basal cell layer (4). The clinical importance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN is strongly predictive of adenocarcinoma, and its identification in biopsy specimens of the prostate warrants further searches for concurrent cancer. PIN alone has no apparent influence on prostatic serum antigen concentration, and it is not apparently visible with current imaging techniques. Patients with PIN may be ideal candidates for chemoprevention trials. This series of reports addresses all current aspects of PIN, including diagnostic criteria, epidemiology and presumptive etiology, molecular biology, clinical significance and feasibility of prevention. Workgroup 1 reiterated the importance of strict adherence to diagnostic criteria for PIN, particularly high-grade PIN, in order to ensure comparison of results among pathologists. Other putative precursors were discussed, but their role is uncertain or doubtful for most prostate cancers. Workgroup 2 focused on the epidemiology of PIN and its prevalence in different populations. Consensus was reached that high-grade PIN increases in prevalence with age, and the frequency and extent of PIN are greater in African Americans and African Brazilians than in their white counterparts. The causes of these differences are uncertain. Workgroup 3 examined the molecular biology of PIN, with special emphasis on genetic instability and the close association between high-grade PIN and prostatic adenocarcinoma. The role of family history was considered, but the current evidence is inconclusive regarding PIN and family risk. Workgroup 4 formulated practical clinical guidelines for managing patients with high-grade PIN, noting that the predictive value of this lesion for cancer is very high. Repeat biopsy appears to be indicated in most men who are candidates for curative therapy if they are subsequently found to have cancer, with sampling of both sides of the prostate recommended to optimize cancer detection. Workgroup 5 presented the role of PIN as a target for chemoprevention. The premise of preventing prostate cancer is based on the presumptive role of PIN as a precursor; simply put, does elimination of the putative