Loss of heterozygosity and microsatellite instability at chromosomal sites1q and 10q in morphologically distinct regions of late stage prostate lesions

Purpose: We investigated the incidence of loss of heterozygosity (LOH) and microsatellite instability in sporadic prostate cancer and surrounding tiss ue at loci encompassing the HPC1 and PTEN genes. Materials and Methods: Surgical specimens from 63 patients with sporadic st age T3 or T4 prostatic adenocarcinoma were analyzed for LOH and microsatell ite instability. Microdissected tissue included morphologically normal foci , benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma. LOH anal ysis was performed using 4 microsatellite markers that map in the region of the 1q24 to 25 locus of the putative prostate cancer susceptibility gene H PC1 and 4 that map in the region of the 10q23 locus of the PTEN gene. Results: The incidence of LOH on 10q was consistent with that previously re ported in prostatic tumors. LOH associated with the PTEN locus was recorded in morphologically normal foci, BPH and adenocarcinoma. Sequence analysis of PTEN in a limited number of lesions revealed mutations in nontumor and t umor tissue. Analysis of the DS10215 locus showed significant LOH in tumor but not in benign tissue, suggestive of a tumor suppressor gene in this reg ion associated with prostatic neoplastic progression. In contrast, no signi ficant LOH was observed in the same tissues at 4 loci on chromosome 1q. In this study we recorded elevated levels of microsatellite instability in ben ign prostatic tissue with an additional increase associated with prostatic adenocarcinoma. Conclusions: The low incidence of LOH in the region of the HPC1 locus in al l prostate lesions studied suggests that this putative hereditary prostate cancer susceptibility locus does not appear to have a role in sporadic pros tate cancer, at least not in the context of LOH. In contrast, analysis of t he same tissues for LOH at chromosome 10q confirmed frequent alterations in this region linked to late stage prostate cancer. PTEN mutations in microd issected morphologically normal and BPH tissue showed alterations in nontum or tissue surrounding adenocarcinoma. Microsatellite instability was increa sed in adenocarcinomas over an elevated background recorded in surrounding tissues.