Dataset Information

Diagnostic value of mutation-specific antibodies for immunohistochemical detection of epidermal growth factor receptor mutations in non-small cell lung cancer: a meta-analysis.

ABSTRACT: 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.

SUBMITTER: Chen Z

PROVIDER: S-EPMC4159133 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Diagnostic value of mutation-specific antibodies for immunohistochemical detection of epidermal growth factor receptor mutations in non-small cell lung cancer: a meta-analysis.

Chen Zi Z Liu Hong-bing HB Yu Chun-hua CH Wang Ying Y Wang Li L Song Yong Y

PloS one 20140909 9

<h4>Background</h4>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.<h4>Methods</h4>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 explora ...[more]

PMID: 25203004

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Project description:BackgroundEpidermal growth factor receptor (EGFR) mutation status is the most valuable indicator in the screening of non-small-cell lung cancer (NSCLC) patients for tyrosine kinase inhibitor (TKI) therapy. Accurate, rapid and economical methods of detecting EGFR mutations have become important. The use of two mutation-specific antibodies targeting the delE746-A750 mutation in exon 19 and L858R mutation in exon 21 makes this task possible, but the lack of consensually acceptable criteria for positive results limits the application of this antibody based mutation detection.MethodsWe collected 399 specimens from NSCLC patients (145 resection specimens, 220 biopsy specimens, and 34 cytology specimens) whose EGFR mutation status had been detected by TaqMan PCR assay. Immunohistochemical (IHC) analyses using EGFR mutation-specific antibodies were employed for all samples. After staining and scoring, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated in accordance with different levels of positive grades in comparison with the results of PCR-based assay.ResultsIn IHC-based analyses, 144 cases were scored 0, 104 cases were scored 1+, 103 cases were scored 2+, and 48 cases were scored 3+. With the molecular-based results were set as the "gold standard", the prevalence of mutation was 6.94% (10/144), 23.08% (24/104), 67.96% (70/103) and 100% (48/48), respectively, for samples with scores 0, 1+, 2+ and 3+. When score 3+ was considered positive, the specificity and PPV were 100%; if only score 0 was considered negative, 93.06% NPV was obtained.ConclusionPatients with score 3+ have a perfect PPV (100%), and may accept TKI treatment directly without any molecular-based assays. Patients with score 0 had high NPV (93.06%), which could reach 97.22% when the detection of total EGFR was applied. However, samples with score 1+ or 2+ are unreliable and need further verification of EGFR mutation status by molecular-based assays.

Project description:BackgroundNumerous individual studies have investigated the diagnostic value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection for nasopharyngeal carcinoma (NPC), but the conclusions remain controversial. This meta-analysis aimed to determine the value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection in the diagnosis of NPC.MethodsPROSPERO registration number: CRD42019145532. PubMed, EMBASE, Cochrane Library, and Chinese data libraries (Wanfang, CNKI, and CBM) were searched up to January 2019. The pooled sensitivity, specificity, and positive likelihood, negative likelihood, and diagnostic odds ratios were conducted in this meta-analysis. Summary receiver operating characteristic curves evaluated the test-performance global summary. Publication bias was examined by Deek's funnel plot asymmetry test.ResultsForty-seven studies with 8382 NPC patients (NPC group) and 15,089 individuals without NPC (Control group) were included in this meta-analysis. The sensitivity, specificity, positive likelihood (+?LR), negative likelihood (-LR), DOR and AUC of EBV-DNA in diagnosis of NPC were: 0.76 (95% CI 0.73-0.77), 0.96 (95% CI 0.95-0.97), 14.66 (95% CI 9.97-21.55), 0.19 (95% CI 0.13-0.28), 84 (95% CI 50.45-139.88), 0.96 (SE: 0.001), and 0.55 (95% CI 0.54-0.57), 0.96 (95% CI 0.96-0.97), 12.91 (95% CI 9.55-17.45), 0.35 (95% CI 0.29-0.43), 39.57 (95% CI 26.44-59.23), 0.94 (SE: 0.002) for the EA-IgA, and 0.85 (95% CI 0.84-0.85), 0.89 (95% CI 0.88-0.89), 6.73 (95% CI5.38-8.43), 0.17 (95% CI 0.12-0.23), 43.03 (95% CI 31.51-58.76), 0.93 (SE: 0.007) for the VCA-IgA, and 0.86 (95% CI 0.85-0.88), 0.87 (95% CI 0.88-0.90), 7.55 (95% CI 5.79-9.87), 0.16 (95% CI 0.13-0.19), 50.95 (95% CI 34.35-75.57), 0.94 (SE: 0.008) for the EBNA1-IgA, and 0.70 (95% CI 0.69-0.71), 0.94 (95% CI 0.94-0.95), 9.84 (95% CI 8.40-11.54), 0.25 (95% CI 0.21-0.31), 40.59 (95% CI 32.09-51.35), 0.95 (SE: 0.005) for the Rta-IgG. The EBV-DNA had larger AUC compared with other EBV-based antibodies (P?<?0.05), while the difference between EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG was not statistically significant (P?>?0.05).ConclusionsEBV-DNA, VCA-IgA, EBNA1-IgA and Rta-IgG detection have high accuracy in early diagnosis NPC. In addition, EBV-DNA detection has the higher diagnosis accuracy in NPC. On the other hand, EA-IgA is suitable for the diagnosis but not NPC screening.

Dataset Information

Diagnostic value of mutation-specific antibodies for immunohistochemical detection of epidermal growth factor receptor mutations in non-small cell lung cancer: a meta-analysis.

Publications

Diagnostic value of mutation-specific antibodies for immunohistochemical detection of epidermal growth factor receptor mutations in non-small cell lung cancer: a meta-analysis.

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