Background: Lung cancers are the leading cause of cancer-related deaths worldwide. Surgical resection alone remains preferred treatment for early stage patients with non-small cell lung cancer (NSCLC), whereas surgery plus platinum-based adjuvant chemotherapy is recommended for stages II - IIIa. Despite wide spectrum of known genetic alterations, there is a lack of biomarkers predicting response to adjuvant therapy. The aim of our study was to determine the predictive role of selected gene alterations. Methods and patients: Formalin-fixed paraffin embedded tumor samples were obtained from 209 NSCLC patients with stage I to IIIa. Of these, 59 patients were treated by surgical resection only, the follow-up adjuvant chemotherapy was indicated in remaining 150 cases. There were 146 males and 63 females (mean age 66; range 29-82 years), tumor histology revealed 79 adenocarcinomas, 105 squamous cell carcinomas, 21 large cell carcinomas, two adenosquamous carcinomas and two sarcomatoid carcinomas. Fluorescent in situ hybridization (FISH) was used for evaluation of EGFR, CMYC, MET and FGFR1 gene copy numbers and ALK and ROS1 copy numbers and rearrangements, respectively. EGFR, KRAS and BRAF mutations were screened using Cobas EGFR Mutation Test (Roche), TheraScreen: KRAS Mutation kit (Qiagen) and BRAF p.Val600Glu kit (IntellMed). Results: In the group of 150 resectable NSCLC patients treated with platinum-based adjuvant therapy, increased copy number of EGFR gene predicted poor overall survival (OS) (p = 0.00001, hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.32-2.10) as well as disease-free survival (DFS) (p = 0.0001, HR 1.54, 95% CI 1.23-1.91) in univariate analysis. In multivariate analysis adjusted to age and stage, the EGFR copy number was independent predictor of OS (p = 0.001) as well as DFS (p = 0.0004). In the group of 59 patients treated by surgical therapy only, no correlation of tested markers with clinical-pathological data was identified. Conclusions: Increased copy number of EGFR gene was found to be an independent predictor of outcome in NSCLC patients treated by adjuvant platinum-based therapy. Acknowledgment: This work was financially supported by NPU LO1304, TE02000058 and EATRIS-CZ.
Citation Format: Vladimira Koudelakova, Radek Trojanec, Jana Potockova, Jiri Drabek, Jana Stranska, Petra Smickova, Pavla Kourilova, Ivona Grygarkova, Vitezslav Kolek, Jozef Skarda, Marian Hajduch. Increased copy number of EGFR gene is an independent outcome predictor in resected non-small cell lung cancer patients treated by adjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2643.