8.3%) which is also in accordance with Lee et al. tissues were analyzed in a tissue microarray format employing immunohistochemistry with four different antibodies including Dako PharmDx kit (clone 2-18C9), clone 31G7, clone 2.1E1 and clone SP84 using three different scoring methods. Protein expression was DNA2 inhibitor C5 compared to FISH utilizing two different probes. == Results == EGFR protein expression determined by IHC with Dako PharmDx kit, clone 31G7 and clone 2.1E1 (p 0.05) correlated significantly with both FISH probes independently of the three scoring methods; best correlation is shown for 31G7 using the scoring method that defined EGFR positivity when 10% of the tumor cells DNA2 inhibitor C5 show membranous staining of moderate and severe intensity (p = 0.001). == Conclusion == Overall, our data show differences in EGFR expression determined by IHC, due to the applied antibody. Highest concordance with FISH is shown for antibody clone 31G7, evaluated with score B (p = 0.001). On this account, this antibody clone might by utilized for standard evaluation of EGFR expression by IHC. == Virtual slides == The virtual slide(s) DNA2 inhibitor C5 for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_165. Keywords:Non-small cell lung malignancy (NSCLC), Epidermal Growth Factor Receptor (EGFR), Immunohistochemistry, Fluorescence in Situ Hybridization, Antibody clones == Background == Lung malignancy is the leading cause of death related to cancer in the world according to WHO data published in December 2013. Non-small cell lung malignancy (NSCLC) accounts about 85% of all lung cancers [1]. Despite therapeutic advances, the overall 5-year survival is only 15% [2]. EGFR is a cell surface tyrosine DNA2 inhibitor C5 kinase receptor abundantly expressed on all epithelial and stromal cells [3]. Expression of EGFR is usually deregulated in a variety of solid tumors and has been correlated with disease progression and poor survival [4]. In 34% to 84% of NSCLC patients, EGFR overexpression is also detectable; an increased expression of EGFR is usually proposed to be of prognostic and also of potential predictive relevance [5]. High EGFR gene copy numbers are found in almost 60% of the patients [6]. Based on its central role in cellular tumor growth, EGFR is intended as favored drug target for the Mmp23 development of specific anti-NSCLC treatments [7]. Plenty of EGFR specific therapeutics have been developed and tested in clinical trials; including specific antibodies such as cetuximab and necitumumab, as well as small molecule tyrosine kinase inhibitors (TKI) like erlotinib, afatinib, and gefitinib [8]. The identification of patients who might profit from these selective drugs is of huge interest. Although EGFR targeted therapies have been approved, there exists no general consensus concerning the evaluation of EGFR expression patterns in NSCLC. As shown in the FLEX-study (First Collection Treatment for Patients with EGFR-expressing Advanced NSCLC), high EGFR H-scores can predict survival benefit for cetuximab plus first-line chemotherapy in patients with advanced NSCLC [9]. Due to the prognostic role of EGFR and the relevance of determination the EGFR expression status as well as the identification of EGFR mutations to select individual therapies for lung malignancy patients, the evaluation of lung carcinomas require the optimal characterization of clinical sections in routine histopathology. Thus, it DNA2 inhibitor C5 is of great relevance to determine the specific EGFR status to identify patients for appropriate therapies. With the ongoing progress in generation of EGFR-specific therapeutics, pathologists have to employ standardized protocols for defined antibodies used for immunohistochemical detection of EGFR expression as well as consistent scoring systems. So far, determination of EGFR status was performed by immunohistochemistry on paraffin-embedded tumor specimens to select patients suitable for EGFR-specific therapies. However, this method depends highly on the choice of the first antibody and.