克里唑蒂尼
间变性淋巴瘤激酶
基因重排
荧光原位杂交
医学
活检
碱性抑制剂
病理
间变性大细胞淋巴瘤
免疫组织化学
癌症研究
淋巴瘤
肺癌
生物
基因
遗传学
染色体
恶性胸腔积液
作者
Hideyuki Abe,Akihiko Kawahara,Koichi Azuma,Tomoki Taira,Yoshiaki Takase,Chihiro Fukumitsu,Kazuya Murata,Tomohiko Yamaguchi,Jun Akiba,Hidenobu Ishii,Isamu Okamoto,Tomoaki Hoshino,Sinzo Takamori,Masayoshi Kage
标识
DOI:10.1097/jto.0000000000000507
摘要
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 (<4% rearrangement detected).ResultsOf a total of 64 tumor observation areas from nine excision specimens, 50 areas were positive for ALK gene rearrangement (81.8%). In the comparison of excision and small biopsy samples, all excision specimens were ALK FISH-positive (100%; 6 of 6), whereas only three of the small biopsy samples in these patients were positive (50%; 3 of 6), two were equivocal (33%; 2 of 6), and one was negative (17%; 1 of 6). The two equivocal patients received crizotinib and showed a response.ConclusionALK gene rearrangement heterogeneity was observed in NSCLC specimens by FISH. Our findings suggested that IHC-positive/FISH-equivocal cases should not be considered true "false-negatives" when a small biopsy sample was used for ALK analysis.
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