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━━ Background. The echinoderm microtubule-associated protein-like 4 gene with the 3’ end of the anaplastic lymphoma kinase gene (EML4-ALK fusion gene) is present in 5% of patients with non-small cell lung cancer. This fusion gene is an important predictive factor for making a quick and accurate diagnosis of ALK lung cancer in order to facilitate individual treatment, as patients with this gene respond to crizotinib, an ALK inhibitor. In such cases, screening using the highly sensitive immunohistochemistry (IHC) method and a diagnostic algorithm confirmed on fluorescence in situ hybridization (FISH) is used to diagnose ALK lung cancer. However, we herein report a case involving inconsistent test results obtained using these methods. Case. The patient was a 70year-old, non-smoking female with a histopathological diagnosis of moderately differentiated adenocarcinoma with a ductal structure and mucus production, clinical stage cT2aN3M1b stage IV, on a bronchoscopic biopsy. Her epidermal growth factor receptor (EGFR) mutation status was wild-type; however, she exhibited a strong positive expression on the highly sensitive IHC method compared to a negative expression on a FISH analysis (positive cells: 2 50) according to consecutive ALK examinations of the specimen. On 4’6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, a yellowish structure was identified around the cell nucleus. The submitted specimen was considered to be insufficient for enzyme treatment prior to hybridization, although a reexamination of the specimen using an extending enzyme treatment time showed a positive result (29 50). Tumor shrinkage was consequently noted following the administration of crizotinib. Conclusions. We herein reported a case of EML4-ALK-positive lung cancer with different ALK results between the first and second examinations. (JJLC. 2014;54:206-211) KEY WORDS━━ IHC, FISH, EML4-ALK Reprints: Utae Katsushima, Department of Clinical Oncology, Osaka City General Hospital, 2-13-22 Miyakojimahondori, Miyakojimaku, Osaka 534-0021, Japan. Received April 17, 2014; accepted June 21, 2014. 要旨━━背景.EML4-ALK融合遺伝子は非小細胞肺癌 の約 5%に存在し,ALK阻害薬であるクリゾチニブに奏 効し,個別化治療を進めるうえで正確,迅速なALK肺癌 の診断が重要である.我々は,再検査で異なるFISH結果 が得られたALK肺癌の症例を経験したので報告する. 症例.症例は非喫煙者の 70 歳女性.気管支鏡生検の病理 組織診断は腺管構造と粘液産生を認める中分化型腺癌 で,臨床病期は cT2aN3M1b,stage IV であった.EGFR 遺伝子変異は野生型であり,ALK検索を同検体で行った ところ,高感度 IHC法では強陽性,FISH法では陰性陽性 細胞(2 50 個)であった.提出した標本の染色の状態を 見直すとハイブリダイゼーション前の酵素処理が不十分 であることが示唆されたため,酵素処理時間を延長して 同検体で再検した結果,陽性(29 50 個)と判定された. クリゾチニブの投与により腫瘍縮小効果を認めた.結 論.再検査にて異なるFISH結果が得られたEML4大阪市立総合医療センター 1臨床腫瘍科,2病理診断科. 別刷請求先:勝島詩恵,大阪市立総合医療センター臨床腫瘍科, 〒534-0021 大阪市都島区都島本通 2丁目 13 番 22 号. 受付日:2014 年 4 月 17 日,採択日:2014 年 6 月 21 日. (肺癌.2014;54:206-211) 2014 The Japan Lung Cancer Society Different ALK Results Between First and Reexamination―Katsushima et al Japanese Journal of Lung Cancer―Vol 54, No 4, Aug 20, 2014―www.haigan.gr.jp 207 ALK融合遺伝子陽性肺癌の 1例を経験した. 索引用語━━ IHC,FISH,EML4-ALK

Different ALK Results Between Two Examinations in a Case of EML4-ALK-positive Lung Cancer