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

Houang, Michelle1,2,3; Sioson, Loretta1,2; Clarkson, Adele1,2; Watson, Nicole1; Farzin, Mahtab1,2; Toon, Christopher W.1,3,4; Raut, Aditi3; O’Toole, Sandra A.3,5,6; Cooper, Wendy A.3,5,6; Pavlakis, Nick3,7; Mead, Scott8,9,10; Chou, Angela1,9,10; Gill, Anthony J.1,2,3

Pathology - Journal of the RCPA: October 2014 - Volume 46 - Issue 6 - p 501–508
doi: 10.1097/PAT.0000000000000141

Summary: 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.

1Cancer Diagnosis and Pathology Group, Northern Translational Cancer Research Unit, Kolling Institute of Medical Research, St Leonards

2Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards

3Sydney Medical School, University of Sydney, Sydney

4HistoPath Pathology, North Ryde

5Tissue Oncology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown

6School of Medicine, University of Western Sydney, Sydney

7Department of Medical Oncology, Royal North Shore Hospital, St Leonards

8Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst

9University of NSW, Sydney

10Department of Anatomical Pathology, SydPath, St Vincent's Hospital, Darlinghurst, NSW, Australia

Address for correspondence: Associate Professor A. J. Gill, Department of Anatomical Pathology, Royal North Shore Hospital, Pacific Highway, St Leonards, NSW 2065, Australia. E-mail:

Received 13 February, 2014

Revised 17 March, 2014

Accepted 21 April, 2014

© 2014 Royal College of Pathologists of Australasia
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