EGFR mutation specific immunohistochemistry is a useful adjunct which helps to identify false negative mutation testing in lung cancer

• Published in: Pathology Vol. 46; no. 6; pp. 501 - 508
• Main Authors: Houang, Michelle, Sioson, Loretta, Clarkson, Adele, Watson, Nicole, Farzin, Mahtab, Toon, Christopher W., Raut, Aditi, O’Toole, Sandra A., Cooper, Wendy A., Pavlakis, Nick, Mead, Scott, Chou, Angela, Gill, Anthony J.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.10.2014
• Subjects: Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Cohort Studies; EGFR immunohistochemistry; EGFR inhibitors; erlotinib; Exons - genetics; False Negative Reactions; Female; gefitininb; Humans; Immunohistochemistry; lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; Middle Aged; Mutation; Prospective Studies; Receptor, Epidermal Growth Factor - genetics; Retrospective Studies; Sensitivity and Specificity; Sequence Analysis, DNA; Sequence Deletion; EGFR immunohistochemistry; lung cancer; gefitininb; EGFR inhibitors; erlotinib
• DOI: 10.1097/PAT.0000000000000141
• ISSN: 0031-3025

Mutations in EGFR guide treatment in non-small cell lung cancer (NSCLC). The most common mutations, exon 19 (delE746-A750) and exon 21 (L858R), can be identified by mutation specific immunohistochemistry (IHC). We present our prospective experience of universal reflex IHC and molecular testing in non-squamous NSCLC in the routine clinical setting. A total of 411 specimens from 332 patients were encountered over two years. Of these, 326 (98%) patients underwent EGFR IHC, 15 (5%) were positive for exon 19 deletions and 27 (8%) for exon 21 (L858R); 244 (73%) patients underwent molecular testing. Seventy-six mutations in 64 patients (19% of all patients encountered; 26% with sufficient material for testing) were identified. These comprised nine exon 18 (G719X) mutations, three also with exon 20 mutations; 24 exon 19 deletions, six also with exon 20 mutations; 23 exon 21 (L858R), three also with exon 20 mutations; and 8 exon 20 alone. All 15 exon 19 IHC positive patients were proven mutated (100% specificity, 63% sensitivity). Twenty-two of 27 exon 21 IHC positive cases were proven mutated while three patients had insufficient material for molecular testing (92% specificity, 96% sensitivity). The overall specificity and sensitivity of IHC for any EGFR mutation was 95% and 58%. Five patients initially thought to be wild type for EGFR but IHC positive underwent repeat molecular testing because of the discrepancy which confirmed the IHC result in three cases (60%). We conclude IHC is very specific but not sensitive. Whilst IHC cannot replace molecular testing, it is a useful adjunct which requires minimal tissue and identifies false negative molecular results which occurred in 5% of our patients with eventually confirmed EGFR mutations.