Immunohistochemical discrimination of wild-type EGFR from EGFRvIII in fixed tumour specimens using anti-EGFR mAbs ICR9 and ICR10

• Published in: British journal of cancer Vol. 106; no. 5; pp. 883 - 888
• Main Authors: Modjtahedi, H, Khelwatty, S A, Kirk, R S, Seddon, A M, Essapen, S, Del Vecchio, C A, Wong, A J, Eccles, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.02.2012; Nature Publishing Group
• Subjects: 631/1647/664/1257; 631/67/1059; 692/699/67/1504/1885; 692/700/1750; Antibodies, Monoclonal - immunology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Cell Line, Tumor; Drug Resistance; Epidemiology; Epidermal growth factor; ErbB Receptors - analysis; ErbB Receptors - genetics; ErbB Receptors - immunology; FDA approval; Humans; Immunohistochemistry; Kinases; Ligands; Lung cancer; Medical prognosis; Medical research; Medical sciences; Molecular Diagnostics; Molecular Medicine; Monoclonal antibodies; Mutant Proteins - analysis; Mutant Proteins - immunology; Neoplasms - chemistry; Neoplasms - diagnosis; Oncology; Paraffin Embedding; Predictive Value of Tests; Proteins; Tumors; United Kingdom > UK; EGFRvIII; EGFR PharmDx; ICR10; immunohistochemistry; EGFR; Antineoplastic agent; Immunohistochemistry; Anatomic pathology; Cancerology; Discrimination; EGFR PharmD; Monoclonal antibody; ICRI0; Wild type; Epidermal growth factor receptor
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.27

Background: The human epidermal growth factor receptor (EGFR) is an important therapeutic target in oncology, and three different types of EGFR inhibitors have been approved for the treatment of cancer patients. However, there has been no clear association between the expression levels of EGFR protein in the tumours determined by the FDA-approved EGFR PharmDx kit (Dako) or other standard anti-EGFR antibodies and the response to the EGFR inhibitors. Method: In this study, we investigated the potential of our anti-EGFR monoclonal antibodies (mAbs; ICR9, ICR10, ICR16) for immunohistochemical diagnosis of wild-type EGFR and/or the type-III deletion mutant form of EGFR (EGFRvIII) in formalin-fixed, paraffin-embedded human tumour specimens. Results: We found that the anti-EGFR mAb in the EGFR PharmDx kit stained both wild-type and EGFRvIII-expressing cells in formalin-fixed, paraffin-embedded sections. This pattern of EGFR immunostaining was also found with our anti-EGFR mAb ICR16. In contrast, mAbs ICR10 and ICR9 were specific for the wild-type EGFR. Conclusion: We conclude that mAbs ICR9 and ICR10 are ideal tools for investigating the expression patterns of wild-type EGFR protein in tumour specimens using immunohistochemistry, and to determine their prognostic significance, as well as predictive value for response to therapy with EGFR antibodies.