O1. EGFR, EML4-ALK and ROS 1 testing in Austrian patients with NSCLC: a multicentre study
Maximilian J. Hochmair1, Sophia Holzer1, Ulrike Setinek1, Andrea Mohn-Staudner1, Klaus Kirchbacher2, Nina Dworan1, Britt-Madeleine Arns3, Andreas Fazekas1, Kurt Patocka4, Otto Chris Burghuber1
Background: Mutations in epidermal growth factor receptor (EGFR), EML4-ALK and ROS1 can clearly impact the treatment decisions for patients with non-small cell lung cancer (NSCLC). The incidence of these mutations in Austria is unknown. The aim of the study was to evaluate the prevalence of EGFR, EML4-ALK and ROS1 mutations in Austrian patients with NSCLC.
Methods: Tumor tissue from bronchoscopy, computed tomography (CT) and ultrasound guided biopsies and surgical specimen with histological type of adenocarcinoma and NSCLC not otherwise specified (NOS) excluding squamous cell carcinoma, large cell carcinoma and neuroendocrine carcinoma were routinely analyzed independent from the tumor staging (reflex testing) for EGFR, EML4-ALK and ROS1 mutations from four hospitals in Austria with high expertise in the management of lung cancer. From January 2010 till July 2014 the EGFR mutation detection was performed with the EGFR mutation Test Kit from Roche on a COBAS 4800. From August 2011 till July 2014 the tumor tissue was analyzed for EML4-ALK with a two-step procedure. First an immunohistochemical staining was done with the Ventana anti ALK (D5F3), Opti View DAB IHC DetectionKit and Opti View Amplifikation Kit® and further on positive cases were tested by ALK FISH (dual colour breakapart FISH/Abbott Vysis®). From January 2014 till July 2014 the tumor tissue was analyzed for ROS1 with a two-step procedure. First an immunohistochemical staining was done with ROS1 D4D6, cell signaling® and further on positive cases were tested by ROS1 FISH (ROS1 -6q22.1 dual colour breakapart probe Zyto Vision®).
Results: A total of 1,999 patients were analyzed for EGFR mutation. An EGFR mutation was found in 256 out of 1,999 patients (12.8%), 211 patients (10.6%) carried an activated mutation (exon 19 Deletion and exon 21 L858R), 1,421 patients were tested for EML4-ALK mutation. EML4-ALK positive immunohistochemical staining was found in 217 patients (15.3%), 32 of these patients (2.3%) showed positive ALK FISH analysis, 294 patients were tested for ROS1 mutation. ROS1 positive immunohistochemical staining was found in two patients (0.7%). Both patients showed positive ROS 1 FISH analysis.
Conclusions: Frequency of EGFR (12.8%), EML4-ALK (2.3%) and ROS1 mutations (0.7%) in Austrian patients with NSCLC was quite similar to other Caucasian peers.
Keywords: Non-small cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR); EML4-ALK; ROS1
doi: 10.3978/j.issn.2218-6751.2014.AB001