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EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy

The selection of colorectal cancer patients for anti-epidermal growth factor receptor (EGFR) antibody therapy is based on the determination of their RAS mutation status—a strongly negative predictive factor—since the protein target, EGFR, is not a reliable predictor of therapeutic response. In this...

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Autores principales: Uhlyarik, Andrea, Piurko, Violetta, Papai, Zsuzsanna, Raso, Erzsebet, Lahm, Erika, Kiss, Edina, Sikter, Marta, Vachaja, Jozsef, Kenessey, Istvan, Timar, Jozsef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139947/
https://www.ncbi.nlm.nih.gov/pubmed/32155907
http://dx.doi.org/10.3390/cancers12030614
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author Uhlyarik, Andrea
Piurko, Violetta
Papai, Zsuzsanna
Raso, Erzsebet
Lahm, Erika
Kiss, Edina
Sikter, Marta
Vachaja, Jozsef
Kenessey, Istvan
Timar, Jozsef
author_facet Uhlyarik, Andrea
Piurko, Violetta
Papai, Zsuzsanna
Raso, Erzsebet
Lahm, Erika
Kiss, Edina
Sikter, Marta
Vachaja, Jozsef
Kenessey, Istvan
Timar, Jozsef
author_sort Uhlyarik, Andrea
collection PubMed
description The selection of colorectal cancer patients for anti-epidermal growth factor receptor (EGFR) antibody therapy is based on the determination of their RAS mutation status—a strongly negative predictive factor—since the protein target, EGFR, is not a reliable predictor of therapeutic response. In this study, we revisited the EGFR protein issue using a cohort of 90 patients with KRAS exon2 wild-type colorectal cancer who have been treated with cetuximab therapy. Twenty-nine of these patients had metastatic tissue available for analysis. The level of EGFR protein expression in the patients was determined by immunohistochemistry and evaluated by H-score (HS) methodology. Progression-free survival (PFS) and overall survival (OS) of the patients were determined according to the EGFR-HS ranges of both the primary and metastatic tissues using Kaplan–Meyer statistics. In the case of primary tumors, EGFR scores lower than HS = 200 were associated with significantly longer OS. In the case of metastatic tissues, all levels lower than the EGFR-HS range chosen were associated with significantly longer OS. These results are explained by the fact that metastatic tissues rarely maintained the expression levels of the primary tumors. On the other hand, high EGFR expression levels in either primary tumors or metastatic tissues were associated with multiple metastatic disease. This suggests a negative prognostic role of EGFR expression. However, in a multivariate analysis, one-sidedness remained a strong independent predictive factor of survival. Previous studies demonstrated that the EGFR expression level depends on sidedness. Therefore, a subgroup analysis of the left- and right-sided cases was performed on both primary and metastatic tissues. In the case of metastic tissues, an analysis confirmed a better OS in low EGFR protein-expressing cases than in high EGFR protein-expressing cases. Collectively, these data suggest that EGFR protein expression is another negative predictive factor of the efficacy of cetuximab therapy of KRAS exon2 wild-type colorectal cancer.
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spelling pubmed-71399472020-04-13 EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy Uhlyarik, Andrea Piurko, Violetta Papai, Zsuzsanna Raso, Erzsebet Lahm, Erika Kiss, Edina Sikter, Marta Vachaja, Jozsef Kenessey, Istvan Timar, Jozsef Cancers (Basel) Article The selection of colorectal cancer patients for anti-epidermal growth factor receptor (EGFR) antibody therapy is based on the determination of their RAS mutation status—a strongly negative predictive factor—since the protein target, EGFR, is not a reliable predictor of therapeutic response. In this study, we revisited the EGFR protein issue using a cohort of 90 patients with KRAS exon2 wild-type colorectal cancer who have been treated with cetuximab therapy. Twenty-nine of these patients had metastatic tissue available for analysis. The level of EGFR protein expression in the patients was determined by immunohistochemistry and evaluated by H-score (HS) methodology. Progression-free survival (PFS) and overall survival (OS) of the patients were determined according to the EGFR-HS ranges of both the primary and metastatic tissues using Kaplan–Meyer statistics. In the case of primary tumors, EGFR scores lower than HS = 200 were associated with significantly longer OS. In the case of metastatic tissues, all levels lower than the EGFR-HS range chosen were associated with significantly longer OS. These results are explained by the fact that metastatic tissues rarely maintained the expression levels of the primary tumors. On the other hand, high EGFR expression levels in either primary tumors or metastatic tissues were associated with multiple metastatic disease. This suggests a negative prognostic role of EGFR expression. However, in a multivariate analysis, one-sidedness remained a strong independent predictive factor of survival. Previous studies demonstrated that the EGFR expression level depends on sidedness. Therefore, a subgroup analysis of the left- and right-sided cases was performed on both primary and metastatic tissues. In the case of metastic tissues, an analysis confirmed a better OS in low EGFR protein-expressing cases than in high EGFR protein-expressing cases. Collectively, these data suggest that EGFR protein expression is another negative predictive factor of the efficacy of cetuximab therapy of KRAS exon2 wild-type colorectal cancer. MDPI 2020-03-06 /pmc/articles/PMC7139947/ /pubmed/32155907 http://dx.doi.org/10.3390/cancers12030614 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Uhlyarik, Andrea
Piurko, Violetta
Papai, Zsuzsanna
Raso, Erzsebet
Lahm, Erika
Kiss, Edina
Sikter, Marta
Vachaja, Jozsef
Kenessey, Istvan
Timar, Jozsef
EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy
title EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy
title_full EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy
title_fullStr EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy
title_full_unstemmed EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy
title_short EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy
title_sort egfr protein expression in kras wild-type metastatic colorectal cancer is another negative predictive factor of the cetuximab therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139947/
https://www.ncbi.nlm.nih.gov/pubmed/32155907
http://dx.doi.org/10.3390/cancers12030614
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