Heterogeneity of Anaplastic Lymphoma Kinase Gene Rearrangement in Non–Small-Cell Lung Carcinomas: A Comparative Study Between Small Biopsy and Excision Samples

IntroductionThe standard diagnostic method for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma receptor tyrosine kinase translocation is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has been reported as a potential method in screening for anaplastic lymphoma kinase (ALK)-positive non–small-cell lung carcinomas (NSCLC), whereas several authors have reported a discordance between FISH and IHC results. We investigated the heterogeneity of ALK gene rearrangement in excision specimens by FISH and also examined whether the FISH score of ALK gene rearrangement corresponded in excision and biopsy samples from the same patient.MethodsTwenty ALK IHC-positive patients including six patients treated with crizotinib therapy were evaluated for the presence of ALK FISH. For evaluation of heterogeneity of ALK gene rearrangement in excision specimens, we defined six to 10 observation areas in each case, and the number of ALK FISH positive observation areas (≥15% rearrangement detected) was investigated. ALK FISH score in small biopsy samples was classified as positive (≥15% rearrangement detected), equivocal (5–14% rearrangement detected), or negative (