P15 Prevalence of EML4- ALK Fusion Gene in Adenocarcinoma Lung Patients by Using Immuno Histo Chemistry

Abstract

An oral ATP- competitive TKI of ALK and c- MET, Crizotinib has shown impressive clinical activity in advanced non–small cell lung cancers especially in the tumors harboring ALK rearrangements. With FISH as the mainstay for detection of ALK rearrangements, the ALK Break Apart FISH Probe Kit (Abbott Molecular, Des Plaines, IL) has become an FDA-approved companion diagnostic for targeted therapy with the ALK inhibitor crizotinib in lung cancers. The objective of this molecular epidemiological study is to estimate the prevalence of EML4-ALK fusion gene using IHC as a cost effective alternative to FISH for Indian patients with adenocarcinoma lung. Patients with NSCLC, adenocarcinoma histology, whose tumors had been tested for EML4-ALK fusion gene using IHC were considered for this study. Permission was obtained from the Ethics committee before the start of the study. Clinical characteristics and treatment details were collected from the patient’s medical records. IHC analysis was performed using a Ventana automated immunostainer (Ventana Medical Systems, Illkirch Graffenstaden, France). Detection was performed using a multimer-technology system with the UltraView Universal DAB detection kit. A total of 204 NSCLC adenocarcinoma patients were included in the study. There were 126 (61.7%) men and 78 (38.23%) women with a median age of 57 years. Of the 204 patients, 47 (23.03%) were non-smokers and 175 (85.78%) had stage-IV disease at the time of initial diagnosis. 48 (23.52%) blocks were positive for EGFR mutations whereas 156 (76.47%) were EGFR wild type. EML4-ALK fusion gene was present in 27 (13.23%) patients whereas 177 (86.76%) tumors were EML4-ALK negative. 25 out of the 27 patients with ALK positivity received Crizotinib therapy. The incidence of EML4-ALK gene fusions (13.23%) in this Indian population is four fold high than the previous reported incidences and supports the claim of several recent studies that a relatively new ALK clone, 5A4 and D5F3 from cell signaling technology (Ventana) can accurately identify ALK rearranged lung ACA as compared to FISH. The inclusion of IHC for the detection of EML4-ALK gene fusions as a low cost alternative seems warranted.