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

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 chem...

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Autores principales: Li, Yaqi, Yao, Qianlan, Zhang, Long, Mo, Shaobo, Cai, Sanjun, Huang, Dan, Peng, Junjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186407/
https://www.ncbi.nlm.nih.gov/pubmed/32926498
http://dx.doi.org/10.1002/ONCO.13521
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author Li, Yaqi
Yao, Qianlan
Zhang, Long
Mo, Shaobo
Cai, Sanjun
Huang, Dan
Peng, Junjie
author_facet Li, Yaqi
Yao, Qianlan
Zhang, Long
Mo, Shaobo
Cai, Sanjun
Huang, Dan
Peng, Junjie
author_sort Li, Yaqi
collection PubMed
description 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.
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spelling pubmed-81864072021-06-15 Immunohistochemistry‐Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer Li, Yaqi Yao, Qianlan Zhang, Long Mo, Shaobo Cai, Sanjun Huang, Dan Peng, Junjie Oncologist Gastrointestinal Cancer 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. John Wiley & Sons, Inc. 2020-09-28 2020-12 /pmc/articles/PMC8186407/ /pubmed/32926498 http://dx.doi.org/10.1002/ONCO.13521 Text en © 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Gastrointestinal Cancer
Li, Yaqi
Yao, Qianlan
Zhang, Long
Mo, Shaobo
Cai, Sanjun
Huang, Dan
Peng, Junjie
Immunohistochemistry‐Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer
title Immunohistochemistry‐Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer
title_full Immunohistochemistry‐Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer
title_fullStr Immunohistochemistry‐Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer
title_full_unstemmed Immunohistochemistry‐Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer
title_short Immunohistochemistry‐Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer
title_sort immunohistochemistry‐based consensus molecular subtypes as a prognostic and predictive biomarker for adjuvant chemotherapy in patients with stage ii colorectal cancer
topic Gastrointestinal Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186407/
https://www.ncbi.nlm.nih.gov/pubmed/32926498
http://dx.doi.org/10.1002/ONCO.13521
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