Analysis of Consensus Molecular Subtypes of Colorectal Cancer in Oman with Clinicopathologic Correlation

Colorectal cancer (CRC) is a major public health challenge in Oman and a leading cause of cancer-related mortality. The rising incidence has been associated with lifestyle changes, urbanization, and genetic factors. The CRC Subtyping Consortium has defined four consensus molecular subtypes (CMS1-CMS4); however, data on their distribution in the Gulf region, including Oman, remain limited. This study aimed to characterize the distribution of CMS subtypes in Omani CRC patients and assess their clinicopathologic correlations using a practical immunohistochemistry (IHC) panel supplemented by a limited targeted molecular approach. This study included 273 CRC patients diagnosed between 2023 and 2024 at two major referral hospitals in Muscat. Initially, the mismatch repair (MMR)-deficient tumors (dMMR) were assigned as CMS1, while the MMR-proficient (pMMR) tumors were further evaluated for β-catenin, P53, KRAS, and TGF-β expression. Mutations in <i>BRAF</i>, <i>TP53</i>, and <i>KRAS</i> were analyzed by sequencing. The cohort comprised 51.6% males, with a mean age of 59.1 years. Most tumors were left-sided (70.7%). dMMR (CMS1) comprised 31 cases (11.35%). Out of the pMMR tumors, 111 cases (40.65%) showed positive expression of β-catenin and P53 (CMS2), 63 cases (23.0%) showed <i>KRAS</i> mutations (CMS3), and 68 cases (24.9%) showed TGF-β-positive expression (CMS4). The cases were predominantly concentrated in Muscat (41%). This study demonstrated the feasibility and clinical relevance of CMS-based classification in Oman and its potential role in precision oncology and healthcare planning.