关键词: 前列腺, 转移, 等位基因失衡, 显微切割, 肿瘤进展

Abstract: Objective To observe the genetic basis of the clonal evolution of prostate carcinoma. Methods The pattern of allelic loss in 25 matching primary and metastatic prostatic adenocarcinoma were analyzed. DNA sample for the analysis of allelic loss pattern were prepared by tissue microdissection. The oligonucleotide primer pairs for the microsatellite DNA markers were D8S133, D8S136, D8S137, ANK1 on chromosome 8p12-21, LPLTET on chromosome 8p22, and D17S855 on chromosome 17q21. Results The overall frequency of allelic imbalance was 79% in primary tumors and 88% in paired metastases. Of 24 informative cases, 14 patients(58%) showed the same pattern of allelic loss or retention in matching primary and metastatic tumor at all marker locus; discordant allelic loss was observed in the remaining 10 patients(42%). Four patients showed loss of the same allele at one or more marker loci and both primary and metastatic tumors, but discordant allelic loss was observed at other marker loci. Five patients showed allelic loss in at least one genetic marker in the metastatic tumor but not in its matching primary tumor. Five patients displayed loss in one or more marker loci in a primary tumor but not in the matching metastases. Conclusion These data suggest that different patterns of allelic deletion may be acquired during cancer progression to metastases. The differences in genetic composition between primary prostate carcinoma and its metastases may be related to intrinsic cancer heterogeneity, overall genetic instability, and clonal divergence.

Key words: prostate, metastasis, allelic disequilibrium, microdissection, tumor progression