ALK rearrangement in a selected population of advanced non-small cell lung cancer patients: FISH and inmunohistochemistry diagnostic methods, prevalence, and clinical outcomes.

Abstract

7566 Background: ALK rearrangement represents a novel molecular target in a subset of non small cell lung cancers (NSCLC). Our aim is to explore fluorescence in situ hibridation (FISH) and inmunohistochemistry (IHC) as diagnostic methods, prevalence and clinical outcomes of ALK rearrangement patients in a selected population of NSCLC. Methods: patients with NSCLC previously screened for EGFR mutation at our institution bettween June 2006 and January 2010 were selected. ALK rearrangement was identified by using FISH and the value of IHC (D5F3 monoclonal antibody-mAb) was explored. For IHC ALK protein expression positivity was defined as tumor-specific staining of any intensity in ≥10% of the tumor cells. Results: 92 patients were identified. Data is available for 71 patients: median age was 61 years (range 36-83), 80% were adenocarcinomas, 7% squamous and 13% NOS carcinomas. 51% patients were female. All were caucasian. 32% of the patients were never smokers and 30% former smokers. 6 (8.5%) patients were ALK rearranged positive by FISH, 9 (12.7%) were EGFR mutant, and 56 (78.8%) were wild type (WT/WT) for both ALK and EGFR. ALK rearrangements and EGFR mutations were mutually exclusive. ALK rearranged patients tend to be younger than EGFR mutated or WT/WT patients (median age of 53, 59 and 62 years, respectively). Patients with ALK positive tumors were predominantly never smokers (67%) and adenocarcinomas (83.4%) with equal distribution for sex. ALK positive and EGFR mutant patients have a better survival than WT/WT patients (p=0.003 and p=0.03). All patients with ALK FISH negative tumors were negative for ALK IHC. Out of 6 patients positive for ALK FISH, 4 were also positive for ALK IHC, 1 negative and in the other there was not enough tissue to perform the analysis. Conclusions: The prevalence of ALK rearrangement is 8.5% in a caucasian selected population of NSCLC. ALK positive patients have different clinical features and a better prognostic than EGFR WT and ALK negative patients. IHC with D5F3 mAb against ALK is a promising method for detecting ALK rearranged NSCLC patients.