Cargando…
Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer
Cetuximab (Cmab), a chimeric monoclonal antibody for targeting the epidermal growth factor receptor, has become one of the standard treatments for metastatic colorectal cancer (mCRC). However, only a small proportion of patients respond to Cmab, and it has been reported that KRAS mutation is a negat...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629210/ https://www.ncbi.nlm.nih.gov/pubmed/23599782 http://dx.doi.org/10.3892/ol.2013.1187 |
_version_ | 1782266544700522496 |
---|---|
author | NAKAMOTO, KENTARO NAGAHARA, HISASHI MAEDA, KIYOSHI NODA, EIJI INOUE, TORU YASHIRO, MASAKAZU NISHIGUCHI, YUKIO OHIRA, MASAICHI HIRAKAWA, KOSEI |
author_facet | NAKAMOTO, KENTARO NAGAHARA, HISASHI MAEDA, KIYOSHI NODA, EIJI INOUE, TORU YASHIRO, MASAKAZU NISHIGUCHI, YUKIO OHIRA, MASAICHI HIRAKAWA, KOSEI |
author_sort | NAKAMOTO, KENTARO |
collection | PubMed |
description | Cetuximab (Cmab), a chimeric monoclonal antibody for targeting the epidermal growth factor receptor, has become one of the standard treatments for metastatic colorectal cancer (mCRC). However, only a small proportion of patients respond to Cmab, and it has been reported that KRAS mutation is a negative biomarker of response to Cmab therapy. The aim of this study was to detect additional biomarkers of response to Cmab therapy in patients with mCRC. We evaluated the effects of Cmab therapy in 36 patients with mCRC according to the Response Evaluation Criteria in Solid Tumors, and classified patients who achieved complete response, partial response or stable disease as responders, and patients who achieved progressive disease as non-responders. We retrospectively examined the difference between the two groups using KRAS analysis and immunohistochemistry to determine the expression of E-cadherin, p53 and Ki67. Nineteen patients were responders, while 17 patients were non-responders. KRAS status and expression of E-cadherin were significantly correlated with the effect of Cmab therapy. Moreover, the expression of E-cadherin was significantly correlated with the effect of Cmab therapy in KRAS wild-type patients. In KRAS mutant-type patients, the expression of E-cadherin did not significantly correlate with the effect of Cmab therapy, but all responders with KRAS mutant-type tumors expressed E-cadherin. Our results indicate that the expression of E-cadherin detected by immunohistochemistry may be a positive predictor of Cmab-based therapy in mCRC, and that a combination of E-cadherin immunohistochemistry and KRAS analysis may be a more sensitive biomarker than KRAS analysis alone. |
format | Online Article Text |
id | pubmed-3629210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-36292102013-04-18 Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer NAKAMOTO, KENTARO NAGAHARA, HISASHI MAEDA, KIYOSHI NODA, EIJI INOUE, TORU YASHIRO, MASAKAZU NISHIGUCHI, YUKIO OHIRA, MASAICHI HIRAKAWA, KOSEI Oncol Lett Articles Cetuximab (Cmab), a chimeric monoclonal antibody for targeting the epidermal growth factor receptor, has become one of the standard treatments for metastatic colorectal cancer (mCRC). However, only a small proportion of patients respond to Cmab, and it has been reported that KRAS mutation is a negative biomarker of response to Cmab therapy. The aim of this study was to detect additional biomarkers of response to Cmab therapy in patients with mCRC. We evaluated the effects of Cmab therapy in 36 patients with mCRC according to the Response Evaluation Criteria in Solid Tumors, and classified patients who achieved complete response, partial response or stable disease as responders, and patients who achieved progressive disease as non-responders. We retrospectively examined the difference between the two groups using KRAS analysis and immunohistochemistry to determine the expression of E-cadherin, p53 and Ki67. Nineteen patients were responders, while 17 patients were non-responders. KRAS status and expression of E-cadherin were significantly correlated with the effect of Cmab therapy. Moreover, the expression of E-cadherin was significantly correlated with the effect of Cmab therapy in KRAS wild-type patients. In KRAS mutant-type patients, the expression of E-cadherin did not significantly correlate with the effect of Cmab therapy, but all responders with KRAS mutant-type tumors expressed E-cadherin. Our results indicate that the expression of E-cadherin detected by immunohistochemistry may be a positive predictor of Cmab-based therapy in mCRC, and that a combination of E-cadherin immunohistochemistry and KRAS analysis may be a more sensitive biomarker than KRAS analysis alone. D.A. Spandidos 2013-04 2013-02-08 /pmc/articles/PMC3629210/ /pubmed/23599782 http://dx.doi.org/10.3892/ol.2013.1187 Text en Copyright © 2013, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles NAKAMOTO, KENTARO NAGAHARA, HISASHI MAEDA, KIYOSHI NODA, EIJI INOUE, TORU YASHIRO, MASAKAZU NISHIGUCHI, YUKIO OHIRA, MASAICHI HIRAKAWA, KOSEI Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer |
title | Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer |
title_full | Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer |
title_fullStr | Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer |
title_full_unstemmed | Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer |
title_short | Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer |
title_sort | expression of e-cadherin and kras mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629210/ https://www.ncbi.nlm.nih.gov/pubmed/23599782 http://dx.doi.org/10.3892/ol.2013.1187 |
work_keys_str_mv | AT nakamotokentaro expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer AT nagaharahisashi expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer AT maedakiyoshi expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer AT nodaeiji expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer AT inouetoru expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer AT yashiromasakazu expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer AT nishiguchiyukio expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer AT ohiramasaichi expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer AT hirakawakosei expressionofecadherinandkrasmutationmayserveasbiomarkersofcetuximabbasedtherapyinmetastaticcolorectalcancer |