Microsatellite instability in multiple colorectal tumors

Tumor multiplicity is a hallmark of hereditary cancers: in the colon-rectum multiple tumors represent 5-10% of all colorectal cancer cases. A portion of these cases belongs to hereditary non-polyposis colorectal cancer (HNPCC ), a genetic cancer syndrome due to mismatch repair (MMR) gene mutations, p henotypically expressed as microsatellite instability (MSI); the majority o f multiple tumors, however, is apparently without any family history. We an alyzed 78 (38 synchronous and 40 metachronous) neoplasms from 37 patients w ith multiple tumors of the large bowel, both HNPCC and sporadic, with the a im of identifying a common genetic basis in multiple tumors. DNA was extrac ted from normal and cancerous formalin-fixed tissue and was analyzed for MS I using 6 markers. Tumors showing MSI in at least 2 of 6 microsatellite loc i were defined as MSI(+). The overall number of MSI(+) tumors was 22 (28.2% of the total). A significant difference in the rate of MSI(+) between HNPC C and sporadic tumors was observed (85% vs. 17%). In the same patients, the MSI phenotype of synchronous tumors (both HNPCC and sporadic) tended to be more concordant than that of the metachronous ones. The higher frequency o f MSI in HNPCC than in sporadic tumors, even when multiple, suggests that t he involvement of MMR genes in the pathogenesis of the sporadic cases may b e uncommon, thus confirming that screening for MSI in multiple colorectal t umors could be a useful tool in the identification of HNPCC in the general population. (C) 1999 Wiley-Liss, Inc.