Testing for anaplastic lymphoma kinase (ALK) rearrangement in lung adenocarcinomas: a multicentre study

Abstract

Aims Non-small cell lung cancer (NSCLC) has the highest cancer-related mortality globally. Rearrangements of ALK in NSCLCs define a subgroup of patients with specific clinical, pathological and molecular characteristics and are associated with sensitivity to an ALK/MET inhibitor, with promising response rates. We aimed to assess the clinical utility of ALK translocation screening and to identify the frequency and clinicopathological features of lung adenocarcinomas harbouring ALK translocations, using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). Methods NSCLC tissue was obtained from patients treated at the Royal Prince Alfred Hospital and Concord Repatriation Hospital, Sydney, and St Vincent’s Hospital and Peter MacCallum Cancer Centre, Melbourne, with a total of 666 cases evaluated. Tissue microarrays were screened using ALK IHC (Clone ALK-1, Dako; Clone 5A4, Novocastra) and ALK break-apart translocation FISH (Abbott Molecular). Results ALK rearrangements were found in six cases (1%) by FISH, which is comparatively lower than other reported frequencies. The 5A4 ALK antibody identified all six ALK positive cases (100% sensitivity). One false negative resulted from the ALK-1 antibody (86% sensitivity). Conclusions We believe ALK IHC represents an effective means of routinely screening selected NSCLC patients for ALK rearrangement testing using FISH.