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 therapeuti...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/3/614 |
| _version_ | 1797724378922745856 |
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| author | Andrea Uhlyarik Violetta Piurko Zsuzsanna Papai Erzsebet Raso Erika Lahm Edina Kiss Marta Sikter Jozsef Vachaja Istvan Kenessey Jozsef Timar |
| author_facet | Andrea Uhlyarik Violetta Piurko Zsuzsanna Papai Erzsebet Raso Erika Lahm Edina Kiss Marta Sikter Jozsef Vachaja Istvan Kenessey Jozsef Timar |
| author_sort | Andrea Uhlyarik |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T10:16:27Z |
| format | Article |
| id | doaj.art-17a247911d9d4e5786c5c608df2a8a0d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T10:16:27Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-17a247911d9d4e5786c5c608df2a8a0d2023-09-02T10:27:24ZengMDPI AGCancers2072-66942020-03-0112361410.3390/cancers12030614cancers12030614EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab TherapyAndrea Uhlyarik0Violetta Piurko1Zsuzsanna Papai2Erzsebet Raso3Erika Lahm4Edina Kiss5Marta Sikter6Jozsef Vachaja7Istvan Kenessey8Jozsef Timar9Department of Oncology, Medical Center, Hungarian Defence Forces, 1065 Budapest, Hungary2nd Department of Pathology, Semmelweis University, 1091 Budapest, HungaryDepartment of Oncology, Medical Center, Hungarian Defence Forces, 1065 Budapest, Hungary2nd Department of Pathology, Semmelweis University, 1091 Budapest, HungaryDepartment of Oncology, Medical Center, Hungarian Defence Forces, 1065 Budapest, HungaryDepartment of Oncology, Medical Center, Hungarian Defence Forces, 1065 Budapest, HungaryDepartment of Oncology, Medical Center, Hungarian Defence Forces, 1065 Budapest, HungaryDepartment of Oncology, Medical Center, Hungarian Defence Forces, 1065 Budapest, Hungary2nd Department of Pathology, Semmelweis University, 1091 Budapest, Hungary2nd Department of Pathology, Semmelweis University, 1091 Budapest, HungaryThe 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.https://www.mdpi.com/2072-6694/12/3/614metastatic colorectal cancercetuximabegfr proteinsurvival |
| spellingShingle | Andrea Uhlyarik Violetta Piurko Zsuzsanna Papai Erzsebet Raso Erika Lahm Edina Kiss Marta Sikter Jozsef Vachaja Istvan Kenessey Jozsef Timar EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy Cancers metastatic colorectal cancer cetuximab egfr protein survival |
| 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 | metastatic colorectal cancer cetuximab egfr protein survival |
| url | https://www.mdpi.com/2072-6694/12/3/614 |
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