Conserved genetic findings in metastatic bladder cancer - A possible utility of allelic loss of chromosomes 9p21 and 17p13 in diagnosis

Context.-Molecular analysis of microsatellite alterations of biologically d istinct tumor cell subpopulations from the same patient may aid in the dete rmination of tumor origin and further our understanding of the genetic basi s of cancer progression. Design.-The authors examined the pattern of allelic loss with polymorphic m icrosatellite markers on chromosome 9p21 (D9S161, D9S171, IFNA), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p5 3 locus, in matched primary and metastatic bladder cancers from 9 patients. All patients underwent cystectomy for bladder cancer and had regional lymp h node metastases at the time of surgery. Genomic DNA was prepared from pri mary cancers and matched synchronous lymph node metastases using a microdis section method. Results.-The overall frequency of allelic loss was 78% in primary cancer an d 89% in paired metastatic cancer. The frequency of allelic loss in the pri mary cancer was 86% with D9S161, 67% with D9S171, 71% with IFNA, and 80% wi th TP53. The frequency of allelic loss in matched metastatic cancer was 100 % with D9S161, 62% with D9S171, 71% with IFNA, and 80% with TP53. An identi cal pattern of allelic imbalance (allelic loss or retention) at multiple DN A loci was observed in matched primary and metastatic carcinoma in 8 (88%) cases. One case showed allelic loss in the metastasis, but not in the prima ry cancer. Conclusions.-The pattern of allelic loss at chromosome 9p21 (p16) and 17p13 (p53) was generally maintained during cancer progression to metastasis, an d identical allelic loss in primary cancer was conserved in paired metastat ic carcinoma. These data suggest that these genetic changes may be useful i n establishing a diagnosis and determining tumor origins in difficult cases .