Abstract 2224: EGFR mutation screening in non-small cell lung cancer: Results from 4 German molecular pathology laboratories

Abstract

Abstract Aims: Somatic mutations in the epidermal growth factor receptor gene (EGFR) have evolved as predictors for sensitivity to EGFR tyrosine kinase inhibitors (TKI) in patients with non-small-cell lung cancer (NSCLC). To date, molecular data underlining the role of EGFR mutations in the tumor as a strong predictor for a better treatment outcome were mostly collected from Asian patients (mutation frequency up to 59.7%). Only one European study (Rosell et al., 2009) verified the predicting power of EGFR mutations in Caucasians living in Europe so far, and reported a notably lower mutation frequency (16.6%) compared to Asian collectives. For Germany, only sparse data are available about the mutation frequency in NSCLC. Here we report the intermediate results from 4 pathology institutes performing quality approved approved EGFR testing certified by the Quality Initiative of the German Society of pathology (QuiP) in non-small cell lung cancer. Material and Methods: Overall, 787 (males: 474, females: 312, n.a.: 1) cases were analysed. The cohort consisted of 782 NSCLC (99.4%) and 5 SCLC (0.6%) selected by attending physicians for EGFR mutation analysis considering TKI treatment. After microdissection, DNA was isolated from serial sections of formalin-fixed, paraffin-embedded tumor tissue after microdissection to obtain at least 70% tumor cells. Exons 18, 19 and 21 of the EGFR gene were analysed using Sanger sequencing. Results: In 72/787 cases (9.2%) an EGFR mutation was detected. Deletions in exon 19 were the most frequent alterations detected (46/72 mutations; 63.9%), followed by point mutations in exon 21 (23/72 mutations; 31.9%). Mutation in exon 18 was a rare event (2/72 mutations; 2.8%). EGFR mutations were significantly associated with adenocarcinomas (p<0.001) (mutation frequency: 11.4%) and female gender (p<0.001). Overall, there was a trend (p=0.052) towards higher age in patients with adenocarcinoma and EGFR mutation compared to cases with EGFR wildtype. This increased age was significantly (p=0.009) associated with an EGFR mutation in female patients. Conclusion: EGFR mutation frequency in this German cohort is lower than reported in Asian or Spanish studies. Mutations in exon 19 were detected more frequently than described in the literature so far. The association with adenocarcinoma histology and female gender could be verified. EGFR mutations seem to be more frequent in patients with higher age. Screening of patients with advanced NSCLC for EGFR mutations is feasible and should be used for improvement of therapy options. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2224. doi:10.1158/1538-7445.AM2011-2224