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Molecular characteristics of colorectal cancer in a Middle Eastern population in a single institution

Tony Ibrahim,a,e Claude Saer-Ghorra,b Vivane Trak-Smayra,b Samah Nadiri,b Charbel Yazbeck,c Maria Baz,d Joseph G. Kattane

From the aDepartment of Medical Oncology, Gustave Roussy, Villejulf, France; bDepartment of Pathology, Faculte de Medecine, Universite Saint-Joseph, Beirut, Lebanon; cDepartment of Gastroenterology, Faculte de Medecine et des Sciences Medicales, Universite Saint-Esprit de Kaslik, Jounieh, Lebanon; dDepartment of Genetics, Faculte de Medecine Site Cochin, Universite Paris Descarte, Paris, France; eDepartment of Hematology-Oncology, Faculte de Medecine, Universite Saint-Joseph, Beirut, Lebanon

How to cite this article:

Ibrahim T, Saer-Ghorra C, Trak-Smayra V, Nadiri S, Yazbeck C, Baz M. Molecular characteristics of colorectal cancer in a Middle Eastern population in a single institution. Ann Saudi Med 2018; 38(4): 251-259.


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.




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