Colorectal Tumors from Different Racial and Ethnic Minorities Have Similar Rates of Mismatch Repair Deficiency (Lynch Syndrome)

abstract

Background and Aims

Microsatellite instability (MSI) in colorectal cancer (CRC) cells results from deficient mismatch repair (MMR) protein function, either acquired or from germline alterations, such as in patients with Lynch Syndrome. Universal screening initiatives for Lynch Syndrome have been encouraged. However, little is known about the true prevalence of MMR deficiency and MSI in colorectal tumors among individuals from different racial and ethnic subgroups or their clinical effects in these populations.

Methods

We performed a retrospective analysis of 253 surgically resected, primary colorectal adenocarcinoma specimens identified from the University of Miami tumor registry from 2005 through 2010. We collected clinical data, including overall survival (OS), the proportion of patients alive at specific intervals, from non-Hispanic White, Hispanic, and Black patients matched by stage. We performed immunohistochemical staining to detect MMR proteins in all specimens and PCR analysis of 51 tumors to detect MSI.

Results

We detected MMR deficiency in 28/253 cases (11.1%), evenly distributed among Blacks (9.6%), non-Hispanic Whites (10.4%), and Hispanics (12.6%) (P=.79). Combined deficiencies in MLH1 and PMS2 were found in 23/28 of MMR deficient samples (82.1%); MSH2 and MSH6 were most frequently absent in tumor samples from Hispanics (P=.03). Eleven of 51 tumor samples (21.6%) had high levels of MSI, and we observed a high level of concordance between MMR and MSI (k=.81). OS was significantly better in patients whose tumors had deficient MMR (hazard ratio for patients with MMR deficient tumors vs MMR proteins intact=0.37; 95% confidence interval, 0.15–0.91; P=.03). Race and ethnicity were not significant predictors of OS.

Conclusions

MMR deficiency in colorectal tumors occurs with similar rates among patients of different racial and ethnic groups, based on an immunohistochemical analysis of 253 primary tumor specimens. This finding indicates the potential value of universal testing of CRC by immunohistochemistry in minority populations and confirms the benefit of MMR deficiency to OS.