Abstract 2261: Prognostic significance of the low level microsatellite instability phenotype differs with race in colorectal adenocarcinoma

Abstract

Abstract Purpose: Several studies have examined the prognostic value of microsatellite instability (low, MSI-L, and high, MSI-H) phenotypes in colorectal adenocarcinomas (CRCs), but none have specifically considered patient race/ethnicity to assess the value of MSI-L. Therefore, this study assessed the prognostic value of the MSI-L phenotype in African-American and non-Hispanic Caucasian (NHCA) CRC patients separately. Experimental Design: CRCs from 276 African-Americans and 377 NHCAs, collected at the hospitals of the University of Alabama at Birmingham and Morehouse School of Medicine, were assessed for microsatellite instability and p53 mutational status (exons 4 through 9). MSI was assessed at 4 CA-dinucleotide MS loci (Mfd 27, Mfd 41, Mfd 47, and Mfd 57) and 2 poly-A repeats (BAT25, BAT26). Samples were considered MSI-H if at least 2 loci showed instability and MSI-L (low) if only 1 marker was unstable. The phenotypes were correlated with clinicopathologic features and patient survival by use of the χ2 test and univariate Kaplan-Meier analyses, respectively. Results: The incidence of the MSI-L phenotype was higher in African-American patients (49 of 276, 18%) compared to NHCA patients (27 of 377, 7%). In contrast, the frequency of the microsatellite stable (MSS) phenotype was higher in CRCs of NHCAs (72%) than in CRCs of African-Americans (56%). In addition, the incidence of microsatellite instability-high (MSI-H) phenotype was similar in African-Americans (26%) and NHCAs (21%). Presence of the MSI-L phenotype significantly correlated with a higher incidence of missense p53 mutations (64%) and high-grade tumors (31%) and with advanced stages (III and IV) (67%) of CRCs in NHCAs. Such associations, however, were not found in African-American patients. For NHCA patients, CRCs with the MSI-L phenotype had significantly higher mortality (log-rank p=0.044) as compared to MSS or MSI-H. In contrast, for African-American patients, the MSI-L phenotype was associated with a better prognosis (log-rank p=0.043) compared to the MSS or MSI-H phenotypes. Conclusions: These findings suggest that CRC with the MSI-L phenotype is associated with p53 mutations, high-grade tumors, and advanced tumor stage, and with short survival of NHCAs but not African-Americans. This work was supported by grants from the NCI/NIH (2U54-CA118948-03, R01-CA98932, and R03-CA139629). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2261. doi:10.1158/1538-7445.AM2011-2261