Consensus molecular subtyping of colorectal cancer by immunohistochemistry, an imperative for a resource limited setting: Report of a Nigerian study

Abstract

Background and Objectives: Studies of colorectal cancer (CRC) molecular heterogeneity have used genome-wide gene expression- based data to group patients into four consensus molecular subtypes (CMS), but the cost and sophistication of analysis has limited its  clinical application. This study aimed at using immunohistochemistry (IHC) to classify CRC specimens in a cohort of patients in Lagos  University Teaching Hospital.

Materials and Methods: Tissue microarrays were constructed from 75 FFPE tissue blocks of CRC. These  were stained for mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2) and four other markers (CDX2, HTR2B, ZEB1, and Ki-6)  by IHC. Semi-quantitative scoring was performed for the other four markers. A panel of CDX2, HTR2B, and ZEB1 was then used to  distinguish between CMS4 and CMS2/CMS3 subtypes, whereas Ki-67 was used to separate CMS2 from CMS3 subtype. MMR status was  used to identify CMS1 subtype.

Results: Of the total evaluable 75 CRC cases, 38% were <40 years old, 60% were males, with mean of 44.8  years (standard deviation [SD] = 16.1). Fifty-nine patients (79%) had microsatellite stable (MSS) tumor, and the remaining 16 (21%) had  microsatellite unstable (MSI) tumor (i.e., CMS1). Thirty-seven (49%) were classified as CMS2 (n = 24) or CMS3 (n = 13) and 22 (29%) of the  cases were classified as CMS4. The CMS4 subtype was significantly more likely to occur among young patients (P < 0.001). CMS1 subtype  was more in patients older than 40 years and 75% of right-sided cancers were CMS1 (P < 0.001).

Conclusion: The study confirms that IHC- based CMS classification and stratification of CRC patients could be a cost-effective prognostic and predictive tool suitable for resource- limited settings.