ABSTRACT
BACKGROUND: The few studies of the molecular biology of colorectal cancer (CRC) in Middle Eastern populations have included only small samples of patients. OBJECTIVE: Evaluate the frequency and prognostic effect of RAS, BRAF, PIK3CA, PTEN, and EGFR somatic mutations as well as mismatch repair (MMR) deficiency in Lebanese Middle Eastern patients. DESIGN: Retrospective single-center descriptive study. SETTING: Lebanese Middle Eastern patients in a tertiary medical cen.ter. METHODS: We included all patients diagnosed with CRC between January 2010 and December 2015, in whom RAS mutational status and the expression of MLH1 and MSH2 proteins were available. MAIN OUTCOME MEASURES: Genetic mutations detected by direct sequencing while MMR protein expression was evaluated by immunohistochemistry. SAMPLE SIZE: 645 patients. RESULTS: RAS, BRAF, EGFR, PI3KCA, and PTEN mutation rates were 38.5%,12.9%, 0%, 11.1% and 0% respectively. The MMR deficiency rate was 20.6%. No factor was associated with RAS mutation whereas MMR-deficient tumors were less likely to be metastatic at diagnosis. Among patients with wild-type RAS females fared better than males (median overall survival [OS]=1734 vs 1079 days respectively, P=.015) even after adjustment for confounding factors by Cox regression analy.sis. This finding was not reproduced in the RAS-mutated group. The median OS of patients with MMR-deficient tumors was not reached, while the median OS was 2475 days in patients who had maintained expression of both MLH1 and MSH2. CONCLUSION: The RAS mutation rate was similar to Western and East Asian countries, but not for the BRAF mutation and MMR deficiency. We also found a prognostic effect for sex in the RAS wild-type group, a finding worthy of further exploration. LIMITATIONS: Retrospective, single center and small sample size. Expression of MSH6 and PMS2 not analyzed. CONFLICT OF INTEREST: None.
