Assessment of EGFR Mutation Status in Lung Adenocarcinoma by Immunohistochemistry Using Antibodies Specific to the Two Major Forms of Mutant EGFR Marie.

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Assessment of EGFR Mutation Status in Lung Adenocarcinoma by Immunohistochemistry Using Antibodies Specific to the Two Major Forms of Mutant EGFR Marie Brevet, Maria Arcila, Marc Ladanyi The Journal of Molecular Diagnostics Volume 12, Issue 2, Pages 169-176 (March 2010) DOI: 10.2353/jmoldx.2010.090140 Copyright © 2010 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

Figure 1 Immunohistochemistry staining of lung adenocarcinoma samples. A: Example of EGFR L858R mutant tumor. Cytokeratin AE1/AE3, total EGFR, and the EGFR L858R mutant–specific antibody show a positive staining, whereas the EGFR Exon 19 deletion mutant–specific antibody is negative. B: Conversely, in a tumor harboring the EGFR Exon 19 15-bp deletion, Cytokeratin AE1/AE3, Total EGFR, and the Exon 19 mutant–specific antibody show a positive staining whereas the EGFR L858R mutant–specific antibody is negative. The Journal of Molecular Diagnostics 2010 12, 169-176DOI: (10.2353/jmoldx.2010.090140) Copyright © 2010 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

Figure 2 Sequenom assay results for EGFR L858R in five cases with positive results by EGFR L858R mutant–specific IHC but negative results with the EGFR L858R PCR-RFLP assay. The H3255 cell line harboring the EGFR L858R mutation is a positive control, whereas the H358 cell line harboring the KRAS 34G/T mutation provides a negative control. A G call is visible, the mutant call (G) is visible at 5378.5 Da and is indicated by an arrow. The germline call (T) is indicated by an asterisk. In tumor samples A and B, only the T call is present and these cases were considered negative. In tumor samples C, D, and E, a mutant peak is present (arrow), confirming the presence of the EGFR L858R mutation. The Journal of Molecular Diagnostics 2010 12, 169-176DOI: (10.2353/jmoldx.2010.090140) Copyright © 2010 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

Figure 3 Possible algorithm for the use of EGFR mutation–specific antibodies. Given its high PPV, IHC with EGFR mutant–specific antibodies could be used as a first pass screening method to identify most lung cancer patients eligible for EGFR-targeted therapy, thereby reducing the overall volume of EGFR molecular testing by an estimated 10 to 15%. The Journal of Molecular Diagnostics 2010 12, 169-176DOI: (10.2353/jmoldx.2010.090140) Copyright © 2010 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions