Journal of Cytology & Histology

Detecting ALK Gene Rearrangements in Lung Cancer Cytology Specimens

Abstract

Cooper WA and O’Toole SA

Molecular testing for EGFR mutations and ALK gene rearrangements has become a routine part of lung cancer pathological diagnosis, and is critical to determine the most effective therapies for patients with this poor prognosis cancer. ALK gene rearrangements are seen particularly in adenocarcinoma of the lung and are associated with an excellent response rate to targeted inhibition with crizotinib in clinical trials for many patients whose tumours harbour this change. ALK gene rearrangement is generally observed at low incidence posing challenges for routine detection. Since a high proportion of lung cancers are inoperable at presentation, cytology plays a central role in diagnosis and provision of material for ALK testing. The advantages offered by cytology specimens for ALK and other molecular testing are becoming increasingly recognised - cytology specimens tend to have a lower proportion of contaminating stromal and other non-neoplastic cells and often have higher quality DNA than routine histology specimens. One challenge is the often limited amount of cytological material obtaining in many lung cancer cytology specimens. FISH testing for ALK gene rearrangement using a break-apart probe is the gold standard for testing although there is a strong role for immunohistochemistry in ALK testing. This review highlights key aspects of ALK testing in cytology specimens.