Mismatch repair protein expression in patients with stage II and III sporadic colorectal cancer.

Abstract

Colorectal cancer (CRC) may be classified according to the level of microsatellite instability exhibited by the tumor. The malignant transformation of normal colonic mucosae to carcinomas may be accelerated by the loss or inactivation of DNA mismatch repair (MMR) genes. The present study examined the expression of certain MMR proteins [namely, MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6) and PMS1 homolog 2 (PMS2)] in patients with stage II and III sporadic CRC. The association between the expression of these proteins, and the clinicopathological characteristics of patients with CRC and their tumors, was investigated. MMR protein expression was examined using immunohistochemistry. MLH1, MSH2, MSH6 and PMS2 protein expression was detected in 78.4% (120/153), 75.2% (115/153), 44.4% (68/153) and 79.7% (122/153) of stage II and III sporadic CRCs, respectively. Additionally, the expression of MLH1 and MSH6 was revealed to be significantly higher in stage III tumors when compared with stage II tumors (P<0.05). MLH1 and MSH6 negative tumors were larger, poorly differentiated and exhibited extraserosal invasion with infrequent lymph node metastasis (P<0.05). Patients with defects in MLH2 and PMS2 also had large tumors that exhibited extraserosal invasion and infrequent lymph node metastasis (P<0.05). No statistically significant associations were observed between MLH1, MSH2, MSH6 or PMS2 protein expression and patient age, sex, tumor localization or angiolymphatic invasion status (P>0.05). From the present study, it was concluded that MMR protein expression status evaluation may increase the efficiency of MMR testing and be useful in improving the individualized approach to patient monitoring and therapy.