HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with <i>RAS</i> Wild Type Metastatic Colorectal Cancer
The overexpressed HER2 is an important target for treatment with monoclonal antibody (mAb) trastuzumab, only in patients with breast and gastric cancers, and is an emerging therapeutic biomarker in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) mAbs cet...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/4/638 |
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| author | Said A. Khelwatty Soozana Puvanenthiran Sharadah Essapen Izhar Bagwan Alan M. Seddon Helmout Modjtahedi |
| author_facet | Said A. Khelwatty Soozana Puvanenthiran Sharadah Essapen Izhar Bagwan Alan M. Seddon Helmout Modjtahedi |
| author_sort | Said A. Khelwatty |
| collection | DOAJ |
| description | The overexpressed HER2 is an important target for treatment with monoclonal antibody (mAb) trastuzumab, only in patients with breast and gastric cancers, and is an emerging therapeutic biomarker in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) mAbs cetuximab and panitumumab. In this study, we investigated the relative expression and predictive value of all human epidermal growth factor receptor (HER) family members in 144 cetuximab-treated patients with wild type <i>RAS</i> mCRC. The relative expression of EGFR and HER2 have also been examined in 21-paired primary tumours and their metastatic sites by immunohistochemistry. Of the 144 cases examined, 25%, 97%, 79%, 48%, and 10% were positive for EGFR, HER2, HER3, and HER4 and all four HER family members, respectively. The expression of EGFR was an indicator of poorer overall survival and the membranous expression of HER2 and HER3 3+ intensity was associated with a shorter progression free survival (PFS). In contrast, the cytoplasmic expression of HER2 was associated with better PFS. In 48% and 71% of the cases, there were discordance in the expression of EGFR or one or more HER family members in paired primary and related metastatic tumours, respectively. Our results implicate the importance of a large prospective investigation of the expression level and predictive value of not only the therapeutic target (i.e., EGFR protein) but also HER2 and other HER family members as therapeutic targets, or for response to therapy with anti-EGFR mAbs and other forms of HER inhibitors, in both the primary tumours and metastatic sites in mCRC. |
| first_indexed | 2024-03-09T05:29:01Z |
| format | Article |
| id | doaj.art-20406664804245d5894a18d830561d8c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T05:29:01Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-20406664804245d5894a18d830561d8c2023-12-03T12:34:08ZengMDPI AGCancers2072-66942021-02-0113463810.3390/cancers13040638HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with <i>RAS</i> Wild Type Metastatic Colorectal CancerSaid A. Khelwatty0Soozana Puvanenthiran1Sharadah Essapen2Izhar Bagwan3Alan M. Seddon4Helmout Modjtahedi5School of Life Science, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UKSchool of Life Science, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UKSchool of Life Science, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UKDepartment of Histopathology, Royal Surrey County Hospital, Guildford GU2 7XX, UKSchool of Life Science, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UKSchool of Life Science, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UKThe overexpressed HER2 is an important target for treatment with monoclonal antibody (mAb) trastuzumab, only in patients with breast and gastric cancers, and is an emerging therapeutic biomarker in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) mAbs cetuximab and panitumumab. In this study, we investigated the relative expression and predictive value of all human epidermal growth factor receptor (HER) family members in 144 cetuximab-treated patients with wild type <i>RAS</i> mCRC. The relative expression of EGFR and HER2 have also been examined in 21-paired primary tumours and their metastatic sites by immunohistochemistry. Of the 144 cases examined, 25%, 97%, 79%, 48%, and 10% were positive for EGFR, HER2, HER3, and HER4 and all four HER family members, respectively. The expression of EGFR was an indicator of poorer overall survival and the membranous expression of HER2 and HER3 3+ intensity was associated with a shorter progression free survival (PFS). In contrast, the cytoplasmic expression of HER2 was associated with better PFS. In 48% and 71% of the cases, there were discordance in the expression of EGFR or one or more HER family members in paired primary and related metastatic tumours, respectively. Our results implicate the importance of a large prospective investigation of the expression level and predictive value of not only the therapeutic target (i.e., EGFR protein) but also HER2 and other HER family members as therapeutic targets, or for response to therapy with anti-EGFR mAbs and other forms of HER inhibitors, in both the primary tumours and metastatic sites in mCRC.https://www.mdpi.com/2072-6694/13/4/638metastatic colorectal cancerHER2cetuximabpredictive biomarker |
| spellingShingle | Said A. Khelwatty Soozana Puvanenthiran Sharadah Essapen Izhar Bagwan Alan M. Seddon Helmout Modjtahedi HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with <i>RAS</i> Wild Type Metastatic Colorectal Cancer Cancers metastatic colorectal cancer HER2 cetuximab predictive biomarker |
| title | HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with <i>RAS</i> Wild Type Metastatic Colorectal Cancer |
| title_full | HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with <i>RAS</i> Wild Type Metastatic Colorectal Cancer |
| title_fullStr | HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with <i>RAS</i> Wild Type Metastatic Colorectal Cancer |
| title_full_unstemmed | HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with <i>RAS</i> Wild Type Metastatic Colorectal Cancer |
| title_short | HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with <i>RAS</i> Wild Type Metastatic Colorectal Cancer |
| title_sort | her2 expression is predictive of survival in cetuximab treated patients with i ras i wild type metastatic colorectal cancer |
| topic | metastatic colorectal cancer HER2 cetuximab predictive biomarker |
| url | https://www.mdpi.com/2072-6694/13/4/638 |
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