Immunohistochemistry-Based Consensus Molecular Subtypes on Tissue Microarray as a Prognostic Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer

Abstract

Background: For stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial. Consensus molecular subtype (CMS) status have been validated to be a prognostic tool for colorectal cancer. In this study, CMS status was investigated as prognostic biomarkers for the efficacy of adjuvant chemotherapy for stage II colorectal cancer. Methods: The tissue microarray (TMA) was retrospectively constructed of 165 non-consecutive, primary, and sporadic stage II CRCs. CMS status was determined by immunohistochemistry staining of CDX2, HTR2B, FRMD6, and ZEB1, combining with MSI testing. The prognostic for adjuvant chemotherapy efficacy of CMS status was calculated by Kaplan-Meier curves and Cox regression analysis. Subgroup analyses were conducted according to tumor location. Findings: CMS status was associated with overall survival (OS, P=0.014) and disease-free survival (DFS, P=0.027) for stage II CRCs and it's an independent risk factor for OS (P=0.029). Among all high-risk clinicopathological factors, patients with CMS2/3 (P=0.010, HR: 0.445, 95%CI: 0.227-0.875), left-sided tumors (P=0.028, HR: 0.488, 95%CI:0.247-0.968) or <12 lymph nodes examined (P=0.015, HR: 0.307, 95%CI: 0.097-0.974) had survival benefit from adjuvant chemotherapy. No survival benefit has been observed for CMS1 or CMS4 tumors. Subgroup analysis stratified by tumor location showed that adjuvant chemotherapy only improved OS for patients with left-sided tumors of CMS2/3 subtype. Regardless of CMS subtype, right-sided tumors had no benefit from adjuvant chemotherapy. Interpretation: For stage II CRCs, CMS subtype is a better prognostic factor for adjuvant chemotherapy. Patients with left-sided tumors of CMS2/3 subtype have OS benefit by receiving adjuvant chemotherapy. Funding: This study is supported by grants from Shanghai Sailing Program (19YF1409500 to YL), Science and Technology Commission of Shanghai Municipality (18401933402 to JP) and Shanghai Natural Science Foundation (19ZR1410200 to DH). Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: This study was approved by the institutional review board of FUSCC, and was carried out in accordance with the Declaration of Helsinki.