Evaluation of a novel surrogate panel for classifying human colorectal carcinomas according to consensus molecular subtypes.

Abstract

Clinical triaging of colorectal carcinomas (CRCs) is essential for prognostication and therapeutic decision-making. Consensus Molecular Subtyping (CMS) was developed for this purpose; however, it requires comprehensive genomic and transcriptomic studies and prediction algorithms, restricting its usage. We examined the utility of a limited surrogate panel of markers for classifying CRCs. We investigated the expression of immunohistochemical markers MLH1, PMS2, MSH2, MSH6, CDX2, HTRB2, FRMD6, and GLUT1, along with reverse transcriptase polymerase chain reaction for KRAS mutation in a retrospective cohort of 100 CRCs. MMR-deficient cases were classified as CMS1. Differential expressions of other markers, alongside consideration of KRAS mutation status as per CMS guidelines, were utilized to classify the tumors into three additional groups. A significant correlation was observed between tumor subtypes and TNM stage groups (P 0.04). While most stage I and II tumors were CMS1 (77.1 %, n-27/35) and CMS2 tumors (91.7 %, n-11/12), stage III and IV tumors were mostly CMS3 (50 %, n-6/12) and CMS4 (44.8 %, n = 13/29) tumors. Our algorithm classified the CRCs into prognostically favorable CMS2/CMS3 types, then unfavorable CMS1/CMS4 types. Notably, However, overall survival and disease-free survivals did not differ as per the individual CMS types. This study highlights the potential of surrogate tumor typing for clinical triaging. However, further research, building on the findings of this study and existing IHC-based classifiers, is essential to develop a more effective and practical surrogate classifier.