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

Abstract

BACKGROUNDThe few studies of the molecular biology of colorectal cancer (CRC) in Middle Eastern populations have included only small samples of patients.OBJECTIVEEvaluate 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.DESIGNRetrospective single-center descriptive study.SETTINGLebanese Middle Eastern patients in a tertiary medical center.METHODSWe 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 MEASURESGenetic mutations detected by direct sequencing while MMR protein expression was evaluated by immunohistochemistry.SAMPLE SIZE645 patients.RESULTSRAS, 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 analysis. 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.CONCLUSIONThe 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.LIMITATIONSRetrospective, single center and small sample size. Expression of MSH6 and PMS2 not analyzed.

Primary Tumor Location and Survival Among Metastatic Colorectal Cancer Patients treated with systemic chemotherapy, and biologic therapies: Retrospective Analysis (2013-2016)

“…However, the mentioned studies used data that represents Asian, North American, and European populations. While the current study con rms that this difference exists in a sample of Middle Eastern populations where multiple mCRC associated factors such as molecular biology of the tumor cells [27] are different than other examined populations in the West. As Ibrahim's study indicated that among colorectal cancer patients in a Middle Eastern sample, the BRAF mutation and MMR de ciency have different characteristics than in Western and East Asian populations [27,28].…”

“…While the current study con rms that this difference exists in a sample of Middle Eastern populations where multiple mCRC associated factors such as molecular biology of the tumor cells [27] are different than other examined populations in the West. As Ibrahim's study indicated that among colorectal cancer patients in a Middle Eastern sample, the BRAF mutation and MMR de ciency have different characteristics than in Western and East Asian populations [27,28]. Thus, this study demonstrated that treatment outcomes of mCRC patients in a sample of the Middle Eastern population are consistent with other populations such as Asian, and Western populations.…”

KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer – practical implications for the clinician

“…The distribution of KRAS mutation among clinical trials was 44.7% in Western European countries, 35.8% in Eastern European countries, while 19.5% of the patients were from the Middle East. Also, in one Middle Eastern study by Zekri et al ., the percentage of mutations ranged from 13% to 45% depending on country 10, 11, 12, 13, 14, 15. Most of the data suggest that geographical distribution is not a significant factor in how such mutations are positioned in the codons.…”

Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer

“…Treatment was carried out for 20 days following the procedure for cell line xenografts (n = 6 mice per group). Using calipers, the growth of the tumors was measured, and the volumes were determined using the formula 1/2 × length × width 2 . The definition of the ethical endpoint was the time point when the dimension of a tumor was 1.5 cm or more on any side.…”

“…Clinically, colorectal cancer (CRC) is a frequently occurring and widely observed malignancy 1,2 . Worldwide, CRC is the third and second most common cancer in male and female patients, respectively, and its mortality rate is the fourth and third highest in these groups, respectively 3,4 .…”