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


METHODS
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.


CONCLUSIONS
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.
School of Life Sciences, Kingston University London, Kingston-upon-Thames, Surrey KT1 2EE, UK. H.Modjtahedi@Kingston.ac.uk
H
H
Modjtahedi
S A
SA
Khelwatty
R S
RS
Kirk
A M
AM
Seddon
S
S
Essapen
C A
CA
Del Vecchio
A J
AJ
Wong
S
S
Eccles
D000911:Antibodies, Monoclonal / Q000276:immunology*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D050505:Mutant Proteins / Q000032:analysis / Q000276:immunology; D009369:Neoplasms / Q000737:chemistry / Q000175:diagnosis*; D016612:Paraffin Embedding; D011237:Predictive Value of Tests
D000911:Antibodies, Monoclonal; D050505:Mutant Proteins; C410723:epidermal growth factor receptor VIII; C512478:EGFR protein, human; D066246:ErbB Receptors