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High specificity but low sensitivity of mutation-specific antibodies against EGFR mutations in non-small-cell lung cancer

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  1. Prospective molecular and morphological assessment of testicular prepubertal-type teratomas in postpubertal men

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  2. The prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer in an unselected, consecutive population

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  3. The morphological growth patterns of colorectal liver metastases are prognostic for overall survival

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  4. K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation

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  1. The prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer in an unselected, consecutive population

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Oxidized resorbable cellulose (Gelita-cel) causing foreign body reaction in the mediastinum

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  3. Schistosomiasis Presenting as Recurring Sigmoid Volvulus in a Danish Man With an Inconspicuous Travel History-A Case Report

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  4. Development of pulmonary tuberculosis following treatment with anti-PD-1 for non-small cell lung cancer

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Determination of epidermal growth factor receptor (EGFR) mutations has a pivotal impact on treatment of non-small-cell lung cancer (NSCLC). A standardized test has not yet been approved. So far, Sanger DNA sequencing has been widely used. Its rather low sensitivity has led to the development of more sensitive methods including real-time PCR (RT-PCR). Immunohistochemistry with mutation-specific antibodies might be a promising detection method. We evaluated 210 samples with NSCLC from an unselected Caucasian population. Extracted DNA was analyzed for EGFR mutations by RT-PCR (Therascreen EGFR PCR kit, Qiagen, UK; reference method). For immunohistochemistry, antibodies against exon19 deletions (clone 6B6), exon21 mutations (clone 43B2) from Cell Signaling Technology (Boston, USA) and EGFR variantIII (clone 218C9) from Dako (Copenhagen, DK) were applied. Protein expression was evaluated, and staining score (multipum of intensity (graded 0-3) and percentages (0-100%) of stained tumor cells) was calculated. Positivity was defined as staining score >0. Specificity of exon19 antibody was 98.8% (95% confidence interval=95.9-99.9%) and of exon21 antibody 97.8% (95% confidence interval=94.4-99.4%). Sensitivity of exon19 antibody was 63.2% (95% confidence interval=38.4-83.7%) and of exon21 antibody was 80.0% (95% confidence interval=44.4-97.5%). Seven exon19 and four exon21 mutations were false negatives (immunohistochemistry negative, RT-PCR positive). Two exon19 and three exon21 mutations were false positive (immunohistochemistry positive, RT-PCR negative). One false positive exon21 mutation had staining score 300. The EGFR variantIII antibody showed no correlation to EGFR mutation status determined by RT-PCR or to EGFR immunohistochemistry. High specificity of the mutation-specific antibodies was demonstrated. However, sensitivity was low, especially for exon19 deletions, and thus these antibodies cannot yet be used as screening method for EGFR mutations in NSCLC. Refinement of sensitivity for the mutation-specific antibodies is warranted to improve molecular diagnosis using EGFR immunohistochemistry.

Original languageEnglish
JournalModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Volume27
Issue number12
Pages (from-to)1590-8
Number of pages9
ISSN0893-3952
DOIs
Publication statusPublished - Dec 2014

ID: 44963908