Clinical management of premalignant lesions of the prostate. WHO Collaborative Project and Consensus Conference on Public Health and Clinical Significance of Premalignant Alterations in the Genitourinary Tract.

The presence of high-grade prostatic intraepithelial neoplasia (PIN) in a prostate biopsy is a considerable risk factor for the presence of prostate cancer, with up to 73% of patients having cancer on rebiopsy. The risk is related to the clinical setting (screening vs urological practice) and patient factors such as prostatic serum antigen (PSA) and findings on digital rectal examination (DRE). Thus, high-grade PIN has serious clinical implications. The aim of this paper is to propose practical guidelines for the clinical management of PIN. Based on current knowledge we recommend that: Only patients considered for curative treatment of prostate cancer be further investigated for a PIN biopsy finding; A palpable nodule or tumor-suspicious transrectal ultrasonography (TRUS) finding, in conjunction with a finding of high-grade PIN on prostate biopsy, should prompt rebiopsy; An elevated PSA level or an elevated PSA density should also warrant repeat biopsy, as the most likely cause of PSA elevation is concomitant prostate cancer; The presence of high-grade PIN on biopsy without concomitant prostate cancer in patients suitable for curative treatment, notwithstanding normal DRE, TRUS or PSA, should prompt repeat biopsies, as the association with prostate cancer is significant; The presence of PIN alone on biopsy does not warrant treatment, as a substantial number of rebiopsies yield only PIN.

Allelic loss of 8p sequences in prostatic intraepithelial neoplasia and carcinoma.

OBJECTIVES: Previous work has suggested that prostatic intraepithelial neoplasia (PIN) may be a premalignant lesion important in tumorigenesis of the prostate. However, to adequately test this hypothesis at the genetic level, it is necessary to determine whether lesions in close proximity demonstrate similar genetic alterations and, hence, whether an "evolutionary" relationship might exist between PIN and tumor in the same prostate. Therefore, the purpose of this study was to examine at least two PIN lesions per prostate (one adjacent to and another distant from malignant lesions in the same prostate) for similarities or differences in the types and frequencies of genetic alterations. METHODS: To accomplish this goal, DNA was extracted from microdissected PIN, tumor, and normal epithelial tissue samples from 48 radical prostatectomies and amplified using polymerase chain reaction techniques at highly polymorphic microsatellite repeat sequences at proximal (D8S87, 8p12) and distal (NEFL, 8p21) loci on the short arm of chromosome 8. PIN specimens were either adjacent to (within one high-power microscopic field [HPF]) or distant from (separated by two or more HPFs) tumor specimens from the same patients. RESULTS: Similar fractional allelic loss frequencies were observed for informative tumor (10 [35%] of 29) and PIN (6 [21%] of 29) samples at the NEFL locus, but allelic loss at the D8S87 locus was observed only in tumors (8 [22%] of 36 informative samples). Moreover, allelic loss at the NEFL locus involved the same allele in 4 cases and different alleles in 3 cases. Interestingly, all 4 cases with the same allele loss were from adjacent PIN and tumor tissues, and all 3 with different allele loss were from distant PIN and tumor. CONCLUSIONS: These results suggest that PIN and invasive cancer share common genetic events (eg, deletion at the NEFL locus) along the same pathway of development in the prostrate.

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 carcinoma of the prostate. We evaluated the evidence for and against PIN as a premalignant lesion and determined guidelines for the clinical management of PIN. MATERIALS AND METHODS: Literature analysis of histopathological, morphometric, phenotypic and molecular genetic evidence of progression and of clinical findings regarding PIN was done. Literature searches were performed on MEDLINE with relevant key words. RESULTS: PIN, like prostate cancer, occurs most frequently in the peripheral zone of the prostate and is usually located in close proximity to prostate 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 hyperplasia. Deoxyribonucleic acid ploidy in PIN follows the aneuploid proportion 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 association of neoplasia and prostate cancer. High grade PIN in core biopsies without concomitant prostate cancer has a substantial risk for prostate cancer in subsequent biopsies (24 to 73%, up to 100% when the digital rectal examination is suspicious) and should cause further biopsy sampling. CONCLUSIONS: There is convincing evidence that PIN is a precursor lesion to prostate cancer, with a close association of PIN and prostate cancer in biopsy and prostatectomy specimens. A biopsy finding of high grade PIN necessitates further investigation in patients who are candidates for radical treatment for localized prostate cancer.