Abstract 1152: Clinical relevance of elevated microsatellite alterations at selected tetranucleotide repeats in colorectal adenocarcinomas

Abstract

Abstract Purpose: Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) are frequently observed in various cancers, including colorectal cancers (CRCs). The incidence of EMAST and its clinical relevance with respect to patient race, however, have not been studied. Therefore, we assessed the frequency and clinical relevance of EMAST and microsatellite instability (MSI) in African-American (AA) and non-Hispanic Caucasian (NHCA) CRC patients. Methods: We analyzed 166 CRCs, collected from the University of Alabama at Birmingham and Grady Memorial hospitals. The EMAST and MSI status of the CRCs was evaluated using seven tetranucleotide microsatellite markers (MYCL1, D8S321, D9S242, D9S747, D20S82, D20S85, L17686) and five National Cancer Institute-recommended MSI markers (BAT25, BAT26, D2S123, D5S346, D17S250). This was accomplished by polymerase chain reactions using marker-specific primers. The status for EMAST and MSI was considered positive if at least two EMAST- or MSI-specific loci were found to be unstable. The EMAST and MSI phenotypes were correlated with clinicopathologic features and patient survival. Results: The overall incidence of EMAST was 46% (77 of 166 cases); AA patients had a higher incidence (62 of 124, 50%) relative to NHCA patients (15 of 42, 36%). Analyses based on tumor location and patient race showed that, for AAs, EMAST was more common in colonic tumors (60 of 114, 53%) than in tumors of NHCAs (10 of 32, 31%). In contrast, only 20% of rectal tumors in AAs (2 of 10) demonstrated EMAST, as compared to NHCA (5 of 10, 50%) patients. Combined analysis (both racial groups) showed that 16% (26 of 166) of cases exhibited both EMAST and the phenotype, MSI-high. Furthermore, for AA patients, but not NHCA patients, EMAST was associated with mucinous CRCs (χ2p = 0.02 and χ2p = 0.56, respectively). NHCA patients who had EMAST had lower median survival (24 months) relative to those without EMAST (55 months). In contrast, the AA patients did not demonstrate an appreciable difference in median survival. Conclusions: These findings suggest that, for AA patients, CRCs with EMAST are associated with the MSI-high phenotype and mucinous tumors. For NHCA patients, EMAST is associated with short survival. This work was supported by grants from the NCI/NIH (2U54-CA118948, R01-CA98932, and R03-CA139629). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1152. doi:1538-7445.AM2012-1152