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IASLC ATLAS OF ALK TESTING IN LUNG CANCER
A new generation of ALK inhibitors has been developed, and these inhibitors are being studied in ongoing clinical trials. As the nature of various gene rearrangements become known, assays using polymerase chain reaction (PCR) and sequencing to detect the fusion genes have been developed. In addition, studies from multiple institutions have shown that ALK protein can be detected by immunohistochemistry (IHC) with signal amplification in almost all tumors that are ALK positive on FISH, and several case reports have also reported that NSCLC tumors harboring atypical ALK patterns on FISH (ALK FISH negative) that are ALK positive on IHC may respond to treatment with ALK inhibitors (Peled 2012). In this context, commercial IHC kits are currently under development and validation. The development of these multiple diagnostic platforms provides alternative methods for laboratories to detect ALK gene rearrangements or fusion proteins, depending on the local availability of technical expertise and equipment. Because clinical diagnostic testing requires assays that can be performed with robust reproducibility and reliability, standardization of these assays is needed. To address this issue, the Pathology Committee of the International Association for the Study of Lung Cancer (IASLC) convened a panel of experts to publish this guide, which can help pathologists, laboratory scientists, and practicing physicians better understand the background, protocol, and interpretation of results of ALK testing in patients with advanced NSCLC.