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

The oncologist

article

Yaqi Li¹  Qianlan Yao³  Long Zhang¹  Shaobo Mo¹  Sanjun Cai¹  Dan Huang³  Junjie Peng¹ 

[1] Department of Colorectal Surgery, Fudan University;Department of Oncology, Shanghai Medical College, Fudan University;Department of Pathology, Fudan University;Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University

关键词: Colorectal cancer;    Consensus molecular subtype;    Tumor location;    Adjuvant chemotherapy;    Stage II;   

DOI  :  10.1002/ONCO.13521

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background For stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial. Consensus molecular subtype (CMS) has been validated to be a prognostic tool for CRCs. In this study, CMS status was investigated as a prognostic biomarker for the efficacy of adjuvant chemotherapy for stage II colorectal cancer. Materials and Methods The tissue microarray was retrospectively constructed of 165 nonconsecutive, primary, and sporadic stage II CRCs. CMS status was determined by immunohistochemistry staining of CDX2, HTR2B, FRMD6, and ZEB1, combining with microsatellite instability 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. Results Kaplan-Meier curves indicated that CMS was associated with overall survival (OS) and disease-free survival for stage II CRCs. Cox regression analysis showed that CMS was an independent risk factor for OS. Among high-risk clinicopathological factors, patients with CMS2/3 (hazard ratio [HR]: 0.445, 95% confidence interval [CI]: 0.227–0.875), left-sided tumors (HR: 0.488, 95% CI: 0.247–0.968), or fewer than 12 lymph nodes examined (HR: 0.307, 95% CI: 0.097–0.974) had survival benefit from adjuvant chemotherapy. Subgroup analysis showed that adjuvant chemotherapy only improved OS for patients with left-sided tumors of CMS2/3 subtype. Regardless of CMS, right-sided tumors had no benefit from adjuvant chemotherapy. Conclusion CMS is a better prognostic factor for adjuvant chemotherapy for stage II CRCs. Together with tumor location, CMS classification will aid in personalized treatment for stage II CRCs. Implications for Practice For stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial, in that its minimal benefit (no more than 5% on average) is considered not worth the toxic effects of the drugs. There are still no effective prognostic and predictive biomarkers. This study showed that consensus molecular subtype (CMS) status is a predictive marker for adjuvant chemotherapy efficacy. Patients with left-sided tumors of CMS2/3 subtype have survival benefit by receiving adjuvant chemotherapy, which will aid in personalized treatment for stage II CRCs. Moreover, this test of CMS based on immunohistochemistry is cheap, not time consuming, and easily conducted in the laboratories of most hospitals.

【 授权许可】

CC BY|CC BY-NC