P1.16 A Study on Clinicopathological Features and Diagnostic Methods of ALK Fusion-Positive Non-Small Cell Lung Cancer in KR

Abstract

Lung cancer is one of the most common malignancies and the leading cause of cancer-related death in Korea. A lot of efforts have been put into to develop new, more effective treatments and biological markers to predict the therapeutic responses, leading to the discovery of various genetic changes, the so-called “growth drivers” of carcinogenesis. Some genetic alterations have become the new treatment targets, and there have been suggestions that different mutations are associated with different clinicopathological characteristics and prognosis. In this study we aimed to evaluate the status of the key “driver” mutation ALK fusion in Korean non-small cell lung cancer patients and its association with the clinicopathological characteristics, including the presence of other genetic mutations. We also compared different methods for ALK fusion detection, i.e., fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and next-generation sequencing (NGS) analyses to find out which method would the most effective. A total of 482 NSCLC patients who underwent ALK FISH test were evaluated for clinicopathological features such as age, sex, smoking history, tumor stage, histological subtype, immunohistochemical profile including ALK, EGFR mutation status and survival. Some ALK FISH-positive and -negative cancers were newly submitted to NGS analysis for DNA and RNA alterations. The ALK fusion-positive tumors were associated with younger age, more female patients, frequent nodal metastases and advanced stage, and short survival. The diagnostic agreement rates among ALK FISH, ALK IHC, and NGS ranged from about 60 to 90% and when considering the patient outcome as a measurement of the test efficacy, the ALK FISH may not be the most reliable one in diagnosis of ALK fusion-positive lung cancer. The NGS analysis detected various additional genetic alterations never considered at the time of diagnosis, including NPM3-TRK rearrangement. Comparing the results of ALK FISH, IHC and NGS, we concluded in practice ALK testing should better be diversified concerning FISH and IHC, and NGS analysis would be a good alternative of ALK FISH with an additional advantage of simultaneous detection of different mutations.