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FIGURE 1. Panels A, C, and E show one case of epithelioid mesothelioma with MET gene amplification. A, hematoxylin and eosin-stained sections (magnification 10×); C, interphase fluorescence in situ hybridization (FISH) analysis showing amplification of MET (white arrows indicate spots of MET red* signal points) with a MET/ CEP7 ratio of 4.0 (approximately eight red signals vs. two green signals; magnification 100×); E, immunohistochemistry (IHC) staining with anti-c-MET antibody showing overexpression on cytoplasm and membrane of MET protein (magnification 40×). Panels B, D and F show one case of epithelioid mesothelioma with wild-type gene status and negative expression of MET protein. B, hematoxylin and eosin 10×; D, FISH for MET gene 100×; F: IHC for MET protein 40×. MET gene amplification was investigated by FISH using the probe MET/CEP7 cocktail (Vysis MET Spectrum Red FISH Probe Kit reagent/ Vysis CEP 7 [D7Z1] SpectrumGreen Probe, both reagents from Abbott Molecular, Des Plaines, IL). IHC staining of MET was performed by Antic-Met Antibody IHC-plus LS-B2812

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BackgroundNon-small-cell lung cancers (NSCLCs) harboring translocations in anaplastic lymphoma kinase (ALK) are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.Case presentationWe describe a case of post-operative local recurrence of lung adenocarcinoma in an 81 year-old male. He underwent radiation and received chemotherapy with docetaxel, but neither treatment regimen was effective. Following identification of ALK rearrangements, crizotinib treatment was initiated. After treatment with crizotinib for 5 days, adverse events including acute renal failure (grade 2/CTCAE ver4.0) and congestive heart failure (grade 3) occurred. Crizotinib modified treatment was required. Half dose of crizotinib treatment could not control tumor progression. Ultimately, crizotinib was administrated at a dose of 250 mg twice daily every 3 day dosing for 13 months with maintenance of the anti-tumor effect.ConclusionThis is the first case report that skip schedule was more effective than dose reduction daily in crizotinib administration for ALK rearranged NSCLC patient with severe adverse events.