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 tumorigenes is 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 di stant from malignant lesions in the same prostate) for similarities or differences in the types and frequencies of genetic alterations. Meth ods. To accomplish this goal, DNA was extracted from microdissected PI N, tumor, and normal epithelial tissue samples from 48 radical prostat ectomies and amplified using polymerase chain reaction techniques at h ighly polymorphic microsatellite repeat sequences at proximal (D8S87, 8p12) and distal (NEFL, 8p21) loci on the short arm of chromosome 8. P IN specimens were either adjacent to (within one high-power microscopi c field [HPF]) or distant from (separated by two or more HPFs) tumor s pecimens from the same patients. Results. Similar fractional allelic l oss frequencies were observed for informative tumor (10 [35%] of 29) a nd 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 ti ssues, 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 th e same pathway of development in the prostrate. (C) 1997, Elsevier Sci ence Inc. All rights reserved.