Mismatch repair protein expression and colorectal cancer in Hispanics from Puerto Rico

Abstract

Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.

Fig. 1

Percentage of Hispanics within the world [42], United States [43], and Puerto Rico [44] populations and their corresponding leading cancer sites in incidence and mortality rates, for men and women [2, 45, 46] in decreasing order. World population 2009 [42]: it is still an underestimation of the actual Hispanic population for not considering those living in non-Hispanic countries, including United States. World Hispanic cancer sites 1998–2002 [45]: based on good quality data provided by United States and Hispanic countries, registries, and populations.

Fig. 2

Immunohistochemistry for MLH1 and MSH2 protein expression (hematoxylin, 400x). (a) Normal colorectal tissue with no antibody staining for MLH1 (negative control). (b) Normal colorectal tissue with MLH1 antibody staining (positive control). (c) Tumor with absence of MLH1 protein expression. (d) Tumor with MLH1 protein expression. (e) Normal colorectal tissue with no antibody staining for MSH2 (negative control). (f) Normal colorectal tissue with MSH2 antibody staining (positive control). (g) Tumor with absence of MSH2 protein expression. (h) Tumor with MSH2 protein expression.