Use of mutation specific antibodies to detect EGFR status in small biopsy and cytology specimens of lung adenocarcinoma Journal Article
| Authors: | Hasanovic, A.; Ang, D.; Moreira, A. L.; Zakowski, M. F. |
| Article Title: | Use of mutation specific antibodies to detect EGFR status in small biopsy and cytology specimens of lung adenocarcinoma |
| Abstract: | Background: EGFR mutation status is the best predictor of response to tyrosine kinase inhibitors (TKIS) in primary lung adenocarcinoma. Approximately 70% of lung cancers are diagnosed in advanced stages where small biopsies and cytological specimens are the only source of material for both diagnosis and mutation testing. Specific antibodies that can detect mutant EGFR protein were evaluated for the detection of EGFR mutation by immunohistochemistry (IHC) in cytology and small biopsy specimens. Methods: Assessment of EGFR mutation status was performed by using antibodies specific to the two major forms of mutant EGFR, exon 21 L858R and exon 19 deletion (15. bp). The study was performed in 145 lung adenocarcinomas, including cytology material, core biopsy, and decalcified bone biopsy. Stains were scored as negative (0), 1+ (weak and focal), 2+ (moderate intensity and focal), and 3+ (strong and diffuse). The result of the IHC stains was correlated with mutations status determined by standard molecular methods. Results: Validation using clinical material showed deletions in exon 19 were detected in 35% and L858R mutation in 17.6% of all cases by standard molecular methods. A cutoff value of 2+ was used as positive by IHC. No wild type cases were immunoreactive. The positive predictive value (PPV) and specificity for both antibodies was 100%. The antibodies performed well in cytology, core biopsies and decalcified bone biopsies. Conclusion: Immunostaining to detect specific mutant EGFR shows a good correlation with mutation analysis and can be used as a screening method to identify patients for TKI therapy. IHC methodology is potentially useful when molecular analysis is not available and for use in small biopsies when material is too scant for molecular tests. Importantly mutation specific antibodies are useful in determining EGFR status in tissues obtained from bone biopsy as decalcification processes used in molecular based studies often result in DNA degradation hindering mutation detection. © 2012 Elsevier Ireland Ltd. |
| Keywords: | immunohistochemistry; human tissue; gene mutation; major clinical study; exon; gene deletion; mutation; exons; molecular genetics; sensitivity and specificity; mutant protein; adenocarcinoma; reproducibility of results; cytology; lung neoplasms; epidermal growth factor receptor; receptor, epidermal growth factor; validation study; mutational analysis; cancer therapy; biopsy; protein tyrosine kinase inhibitor; antibodies, monoclonal; lung adenocarcinoma; immunocytochemistry; diagnosis; antibody specificity; lung biopsy; dna determination; predictive value; antibody screening; dna degradation; cancer antibody; egfr mutation; molecular diagnosis; bone biopsy |
| Journal Title: | Lung Cancer |
| Volume: | 77 |
| Issue: | 2 |
| ISSN: | 0169-5002 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 2012-08-01 |
| Start Page: | 299 |
| End Page: | 305 |
| Language: | English |
| DOI: | 10.1016/j.lungcan.2012.04.004 |
| PROVIDER: | scopus |
| PUBMED: | 22542171 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "CODEN: LUCAE" - "Source: Scopus" |
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