EGFR mutation specific immunohistochemistry is a useful adjunct which helps to identify false negative mutation testing in lung cancer
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.
|ISBN||1465-3931 (Electronic) 0031-3025 (Linking)|
|Authors||Houang, M.; Sioson, L.; Clarkson, A.; Watson, N.; Farzin, M.; Toon, C. W.; Raut, A.; O'Toole, S. A.; Cooper, W. A.; Pavlakis, N.; Mead, S.; Chou, A.; Gill, A. J.;|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/25158821|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12603|