Arun Khattri1, Zhixiang Zuo1, Johannes Brägelmann2, Michaela K Keck1, Mohamed El Dinali1, Christopher D Brown3, Thomas Stricker4, Anish Munagala1, Ezra E W Cohen5, Mark W Lingen6, Kevin P White7, Everett E Vokes5, Tanguy Y Seiwert8. 1. Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA. 2. Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA; Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany. 3. University of Pennsylvania, Philadelphia, PA, USA. 4. Vanderbilt University, Nashville, TN, USA. 5. Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA. 6. Department of Pathology, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA. 7. Institute for Genomics and Systems Biology, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA. 8. Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA; Institute for Genomics and Systems Biology, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA. Electronic address: tseiwert@medicine.bsd.uchicago.edu.
Abstract
BACKGROUND: The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor and is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) cases. The EGFR truncation mutation, EGFR variant III (EGFRvIII), harbors an in-frame deletion of exons 2-7 (801 bp) that leads to the constitutive activation of downstream signaling. EGFRvIII has been reported in ∼40% of glioblastomas (GBM), but its presence in HNSCC remains controversial. METHODS: EGFRvIII deletion in 638 HNSCC samples was analyzed using: (i) quantitative Real-Time polymerase chain reaction (qRT-PCR) on 108 HNSCC samples with direct detection of the EGFRvIII breakpoint, (ii) RNA-Seq analysis on 7 HNSCC tumor tissues and 425 The Cancer Genome Atlas (TCGA) HNSCC samples, and (iii) immunohistochemistry (IHC) for EGFRvIII using an established antibody (L8A4) on a tissue microarray of 105 HNSCC samples. RESULTS: qRT-PCR did not show the presence of EGFRvIII in any of the samples analyzed. Furthermore, we could not detect any EGFRvIII transcripts in the RNA-Seq data of the seven HNSCC samples. However, 2 samples out of 425 TCGA HNSCC samples had EGFRvIII specific reads. EGFRvIII IHC results were assessed as negative for all samples. CONCLUSION: Our results firmly establish that EGFRvIII is very rare in HNSCC as only 2 out of 638 (0.31%) samples we analyzed overall, or 2 out of 540 (0.37%) using mRNA based approaches, were positive for EGFRvIII. EGFRvIII is extremely rare in HNSCC and the clinical significance remains unclear. We propose not to include EGFRvIII testing in regular diagnostic tests for HNSCC.
BACKGROUND: The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor and is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) cases. The EGFR truncation mutation, EGFR variant III (EGFRvIII), harbors an in-frame deletion of exons 2-7 (801 bp) that leads to the constitutive activation of downstream signaling. EGFRvIII has been reported in ∼40% of glioblastomas (GBM), but its presence in HNSCC remains controversial. METHODS: EGFRvIII deletion in 638 HNSCC samples was analyzed using: (i) quantitative Real-Time polymerase chain reaction (qRT-PCR) on 108 HNSCC samples with direct detection of the EGFRvIII breakpoint, (ii) RNA-Seq analysis on 7 HNSCC tumor tissues and 425 The Cancer Genome Atlas (TCGA) HNSCC samples, and (iii) immunohistochemistry (IHC) for EGFRvIII using an established antibody (L8A4) on a tissue microarray of 105 HNSCC samples. RESULTS: qRT-PCR did not show the presence of EGFRvIII in any of the samples analyzed. Furthermore, we could not detect any EGFRvIII transcripts in the RNA-Seq data of the seven HNSCC samples. However, 2 samples out of 425 TCGA HNSCC samples had EGFRvIII specific reads. EGFRvIII IHC results were assessed as negative for all samples. CONCLUSION: Our results firmly establish that EGFRvIII is very rare in HNSCC as only 2 out of 638 (0.31%) samples we analyzed overall, or 2 out of 540 (0.37%) using mRNA based approaches, were positive for EGFRvIII. EGFRvIII is extremely rare in HNSCC and the clinical significance remains unclear. We propose not to include EGFRvIII testing in regular diagnostic tests for HNSCC.
Authors: Mihály Cserepes; Györgyi A Nelhűbel; Mónika Meilinger-Dobra; Adrienn Herczeg; Dóra Türk; Zita Hegedűs; Laura Svajda; Erzsébet Rásó; Andrea Ladányi; Kristóf György Csikó; István Kenessey; Árpád Szöőr; György Vereb; Éva Remenár; József Tóvári Journal: Cancers (Basel) Date: 2022-05-13 Impact factor: 6.575
Authors: Dominik Thomas Koch; Anja Pickhard; Lena Gebel; Anna Maria S Buchberger; Murat Bas; Carolin Mogler; Rudolf Reiter; Guido Piontek; Markus Wirth Journal: Oncotarget Date: 2017-05-16