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EGFR mutant-specific immunohistochemistry has high specificity and sensitivity for detecting targeted activating EGFR mutations in lung adenocarcinoma
  1. W A Cooper1,2,
  2. B Yu3,4,
  3. P Y Yip4,5,6,
  4. C C Ng3,
  5. T Lum1,
  6. M Farzin7,
  7. R J Trent3,4,
  8. B Mercorella3,
  9. A Clarkson7,
  10. M R J Kohonen-Corish2,6,8,
  11. L G Horvath4,5,6,
  12. J G Kench1,4,6,
  13. B McCaughan4,9,
  14. A J Gill4,7,
  15. S A O'Toole1,4,6
  1. 1Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  2. 2School of Medicine, University of Western Sydney, Sydney, New South Wales, Australia
  3. 3Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  4. 4Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
  5. 5Department of Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  6. 6Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, New South Wales, Australia
  7. 7Department of Anatomical Pathology and Northern Cancer Translational Research Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia
  8. 8St Vincent's Clinical School, University of NSW, Sydney, New South Wales, Australia
  9. 9Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  1. Correspondence to Associate Professor Wendy Cooper, Tissue Pathology and Diagnostic Pathology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050, Australia; wendy.cooper{at}sswahs.nsw.gov.au

Abstract

Aim We assessed the diagnostic accuracy of epidermal growth factor receptor (EGFR) mutant-specific antibodies for detecting two common activating EGFR mutations.

Methods Immunohistochemical expression of mutation-specific antibodies against EGFR exon 19 deletion E746-A750 ((c.2235_2249del15 or c.2236_2250del15, p. Glu746_Ala750del) and exon 21 L858R point mutation (c.2573T>G, p.Leu858Arg) were assessed in a cohort of 204 resected early stage node negative lung adenocarcinomas, and protein expression was compared with DNA analysis results from mass spectrometry analysis.

Results Of seven cases with L858R point mutation, six were positive by immunohistochemistry (IHC). There were three false positive cases using L858R IHC (sensitivity 85.7%, specificity 98.5%, positive predictive value 66.7%, negative predictive value 99.5%). All seven E746-A750 exon 19 deletions identified by mutation analysis were positive by IHC. Four additional cases were positive for exon 19 IHC but negative by mutation analysis. The sensitivity of exon 19 IHC for E746-A750 was 100%, specificity 98.0%, positive predictive value 63.6% and negative predictive value 100%.

Conclusions Mutant-specific EGFR IHC has good specificity and sensitivity for identifying targeted activating EGFR mutations. Although inferior to molecular genetic analysis of the EGFR gene, IHC is highly specific and sensitive for the targeted EGFR mutations. The antibodies are likely to be of clinical value in cases where limited tumour material is available, or in situations where molecular genetic analysis is not readily available.

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