ALK Rearrangement Detected by FISH and Inmunohistochemistry Methods. Prevalence and Clinical Outcomes in a Selected Population of Advanced Non Small Cell Lung Cancer Patients
Javier Hernandez-Losa, Pablo Martinez, Josep Castellvi, Tallada Natalia, Teresa Moline, Maria Angeles Montero, Susana Cedres, Victor Rodriguez-Freixinos, Enriqueta Felip, Santiago Ramon y Cajal. Hospital Universitari Vall d´Hebron, Barcelona, Spain; VHIR. Universitat Autónoma de Barcelona, Barcelona, Spain
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 immunohistochemistry (IHC) as diagnostic methods, prevalence and clinical outcomes of ALK rearrangement patients in a selected population of NSCLC.
Design: Patients with NSCLC previously screened for EGFR mutation at our institution between 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: 99 patients were identified with median age was 61.5 years (range 35-83), 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. 7 (7%) patients were ALK rearranged positive by FISH, 13 (13%) were EGFR mutant, and 65 (65.6%) 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 56.7, 63 and 62.3 years, respectively). Patients with ALK positive tumors were predominantly never smokers (71.4%) and adenocarcinomas (71.4%). ALK positive and EGFR mutant patients have a better survival than WT/WT. All patients with ALK FISH negative tumors were negative for ALK IHC. Out of 7 patients positive for ALK FISH, 5 were also positive for ALK IHC, 1 negative and in the other there was not enough tissue to perform the analysis. The ALK FISH positive cases were analyzed by IHC with 5A4 mAb obtaining the same results.
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.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 309, Tuesday Morning