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

Abstract

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.