Diagnostic Value of Mutation-Specific Antibodies for Immunohistochemical Detection of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis

Background Various studies have assessed the diagnostic accuracy of EGFR mutation-specific antibodies in non-small cell lung cancer (NSCLC). We performed a meta-analysis of existing data to investigate the diagnostic value of mutation-specific antibodies for detection of EGFR mutations in NSCLC. Methods We systematically retrieved relevant studies from PubMed, Web of Knowledge, and Google Scholar. Data from studies that met the inclusion criteria were extracted for further exploration of heterogeneity, including calculation of the average sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and analysis of SROC(summary receiver operating characteristic) curves. Results Fifteen studies met our inclusion criteria. A summary of the meta-analysis of the efficacy of the anti-E746-A750 antibody was as follows: sensitivity, 0.60 (95% CI, 0.55–0.64); specificity, 0.98 (95% CI, 0.97–0.98); PLR, 33.50 (95% CI, 13.96–80.39); NLR, 0.39 (95% CI, 0.30–0.51) and DOR, 111.17 (95% CI, 62.22–198.63). A similar meta-analysis was performed for the anti-L858R antibody with results as follows: sensitivity, 0.76 (95% CI, 0.71–0.79); specificity, 0.96 (95% CI, 0.95–0.97); PLR, 24.42 (95% CI, 11.66–51.17); NLR, 0.22 (95% CI, 0.12–0.39) and DOR, 126.66 (95% CI, 54.60–293.82). Conclusion Immunohistochemistry alone is sufficient for the detection of EGFR mutations if the result is positive. Molecular-based analyses are necessary only if the anti-E746-A750 antibody results are negative. Immunohistochemistry seems more suitable for clinical screening for EGFR mutations prior to molecular-based analysis.

[1]  S. O'toole,et al.  EGFR mutant-specific immunohistochemistry has high specificity and sensitivity for detecting targeted activating EGFR mutations in lung adenocarcinoma , 2013, Journal of Clinical Pathology.

[2]  P. Rothberg,et al.  Immunohistochemical detection of mutations in the epidermal growth factor receptor gene in lung adenocarcinomas using mutation-specific antibodies , 2013, Diagnostic Pathology.

[3]  M. Hidalgo,et al.  A Comparison of EGFR Mutation Testing Methods in Lung Carcinoma: Direct Sequencing, Real-time PCR and Immunohistochemistry , 2012, PloS one.

[4]  M. Zakowski,et al.  Use of mutation specific antibodies to detect EGFR status in small biopsy and cytology specimens of lung adenocarcinoma. , 2012, Lung cancer.

[5]  A. Ardizzoni,et al.  EGFR Mutation-specific Antibodies in Pulmonary Adenocarcinoma: A Comparison With DNA Direct Sequencing , 2012, Applied immunohistochemistry & molecular morphology : AIMM.

[6]  P. Validire,et al.  Immunohistochemistry to identify EGFR mutations or ALK rearrangements in patients with lung adenocarcinoma. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  Yih-Leong Chang,et al.  Including Total EGFR Staining in Scoring Improves EGFR Mutations Detection by Mutation-Specific Antibodies and EGFR TKIs Response Prediction , 2011, PloS one.

[8]  Kenji Suzuki,et al.  The usefulness of mutation-specific antibodies in detecting epidermal growth factor receptor mutations and in predicting response to tyrosine kinase inhibitor therapy in lung adenocarcinoma. , 2011, Lung cancer.

[9]  Miguel Angel Molina,et al.  Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer , 2010, Journal of Translational Medicine.

[10]  C. Mathers,et al.  Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 , 2010, International journal of cancer.

[11]  T. Ohira,et al.  Novel Epidermal Growth Factor Receptor Mutation-Specific Antibodies for Non-small Cell Lung Cancer: Immunohistochemistry as a Possible Screening Method for Epidermal Growth Factor Receptor Mutations , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[12]  P. Hofman,et al.  Usefulness of tissue microarrays for assessment of protein expression, gene copy number and mutational status of EGFR in lung adenocarcinoma , 2010, Virchows Archiv.

[13]  Y. Yatabe,et al.  Immunohistochemical Detection of EGFR Mutation Using Mutation-Specific Antibodies in Lung Cancer , 2010, Clinical Cancer Research.

[14]  T. Mitsudomi,et al.  Molecular Diagnosis of Activating EGFR Mutations in Non–Small Cell Lung Cancer Using Mutation-Specific Antibodies for Immunohistochemical Analysis , 2010, Clinical Cancer Research.

[15]  M. Ladanyi,et al.  Assessment of EGFR mutation status in lung adenocarcinoma by immunohistochemistry using antibodies specific to the two major forms of mutant EGFR. , 2010, The Journal of molecular diagnostics : JMD.

[16]  M. Loda,et al.  Mutation-Specific Antibodies for the Detection of EGFR Mutations in Non–Small-Cell Lung Cancer , 2009, Clinical Cancer Research.

[17]  Y. Yatabe,et al.  Epidermal growth factor receptor mutations in lung cancers , 2007, Pathology international.

[18]  D. Haber,et al.  Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  Jonathan J Deeks,et al.  The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. , 2005, Journal of clinical epidemiology.

[20]  Takayuki Kosaka,et al.  Mutations of the Epidermal Growth Factor Receptor Gene in Lung Cancer , 2004, Cancer Research.

[21]  R. Wilson,et al.  EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[23]  Daniel Jones Anticancer drugs: To the rescue? , 2004, Nature Reviews Drug Discovery.

[24]  N. Choudhry,et al.  The conditional relative odds ratio provided less biased results for comparing diagnostic test accuracy in meta-analyses. , 2004, Journal of clinical epidemiology.

[25]  P. Bossuyt,et al.  The diagnostic odds ratio: a single indicator of test performance. , 2003, Journal of clinical epidemiology.

[26]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[27]  C. Gatsonis,et al.  Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative , 2003, BMJ : British Medical Journal.

[28]  Victor M Montori,et al.  Conducting systematic reviews of diagnostic studies: didactic guidelines , 2002, BMC medical research methodology.

[29]  G. Riet,et al.  Systematic reviews of evaluations of diagnostic and screening tests , 2001, BMJ : British Medical Journal.

[30]  Jonathan J Deeks,et al.  Systematic reviews in health care: Systematic reviews of evaluations of diagnostic and screening tests. , 2001, BMJ.

[31]  J. Ioannidis,et al.  Diagnosing acute cardiac ischemia in the emergency department: a systematic review of the accuracy and clinical effect of current technologies. , 2001, Annals of emergency medicine.

[32]  E. Gallagher,et al.  Clinical utility of likelihood ratios. , 1998, Annals of emergency medicine.

[33]  Frederick Mosteller,et al.  Guidelines for Meta-analyses Evaluating Diagnostic Tests , 1994, Annals of Internal Medicine.

[34]  L E Moses,et al.  Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. , 1993, Statistics in medicine.

[35]  Lin Huan,et al.  Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer , 2010 .

[36]  Gerta Rucker,et al.  Bmc Medical Research Methodology Open Access the Relationship between Quality of Research and Citation Frequency , 2006 .