Significance of EGFR expression patterns in patients with non-small cell lung cancer – Evaluation on protein- and/or gene level?

Introduction: Several EGFR-specific molecular inhibitors are currently used in clinical oncology. Thus, the determination of EGFR status on protein level as well as the detection of EGFR mutations to identify patients who show high response rates towards TKIs, is essential. Up to now, common EGFR evaluation criteria are still missing, but absolutely necessary. Aims and objectives: To identify enlarged collectives of patients who might benefit from Tyrosine kinase inhibitors, in addition to those bearing activating mutations, we wanted to figure out which is the optimized method of EGFR expression evaluation on protein level in addition to the determination of gene amplification status. Methods: 206 tumor tissues were analyzed in a tissue microarray format employing immunohistochemistry (IHC) 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 compared to fluorescence in situ hybridization (FISH) using two different probes. Data of IHC and FISH-analysis were further correlated with clinicopathological data to find out, whether IHC could be the method of choice, probably coupled to FISH-analysis. Results: Two different FISH probes revealed identical gene amplification status in NSCLC tumor samples. EGFR protein expression evaluated by IHC correlates significantly with FISH results; best correlation is shown for 31G7 using scoring method B. Conclusion: Our advice is to use Dako PharmDx, 31G7 or 2.1E1 in IHC and confirm these data by FISH analysis to facilitate more patients for EGFR specific treatments concerning their EGFR expression pattern.