Colorectal cancer (CRC) is one of the common cancers in the world. In Saudi Arabia CRC is the most common cancer in males and third most common in females. A newly proposed integrated pathways comprising traditional, alternate and serrated by genetic and epigenetic factors was defined recently and hypothesized to role in the pathogenesis of CRC; however there is a paucity of information about these proposed molecular pathways in different ethnic group. Hence we analyzed a large cohort of Saudi colorectal tumors to understand the role of these molecular pathways. 770 archival CRCs specimen were evaluated for Microsatellite Instability (MSI), BRAF, KRAS and 500 cases for CpG Island Methylator Phenotype (CIMP). Traditional pathway constituted 33.4% of CRC cases; the alternate pathway comprised 11.6% of cases. Strikingly, the serrated molecular pathway accounted for only 0.8% of Middle Eastern CRC that is extremely below compared to publish data. 54.2% CRC cases did not qualify to fit into any pathway and thus were designated an unassigned group. Molecular pathways were significantly associated with tumor site and grade. In our attempt to further classify unassigned group a subset of the uncategorized pathway showed a significant survival difference (p = 0.0079). The Unassigned group that accounted for the majority of our cases reflects the heterogeneity of colorectal cancers and warrants the need to unravel the molecular genetic basis of this disease to further subcategorize these CRC cases. It also identifies the need to do further studies on different populations for better understanding of their exact role and incidence.

Keywords: colorectal; molecular pathways; serrated

Citation Format: Shaham Beg, Sarita Prabhakaran, Rong Bu, Mohammed Al-Assiri, Rami Sairafi, Fouad Al-Dayel, Nasser Al-Sanea, Abdul K. Siraj, Shahab Uddin, Khawla Al-Kuraya. Molecular markers and pathway analysis of Middle Eastern colorectal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2727. doi:10.1158/1538-7445.AM2015-2727