PMC5322209_01
(A) Clinical course. CBDCA: carboplatin, PEM: pemetrexed, Bev: bevacizumab, DOC: docetaxel. (B) Computed tomography images before and after treatment with crizotinib, respectively, showing dramatic response.
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In November 2015, new lesions in the brain, parotid gland, skin, lung, abdominal lymph nodes, and bone were detected (clinical course is shown in Fig. 1A). Within a week, palpable lesions (skin and parotid gland metastases) rapidly shrank; computed tomography showed a dramatic response, with multiple lung metastases almost completely diminished (Fig. 1B).
Tumor histology at initial biopsy (left line) and re-biopsy (right line). Fluorescence in situ hybridization (FISH) with MET probe (red) and chromosome 7 centromere probe (green). Nuclei stained with 4',6-diamidino-2-phenylinodole (blue) ( x 100 magnification) (A). MET/centromere probe of chromosome 7 (CEP7) ratio increased from 0.4 at initial diagnosis to 2.1 at the time of progression; mean MET copy numbers similarly increased from 3.1 to 8.8 copies per cell. Immunohistochemical stains with phosphorylated EGFR (pEGFR; Tyr1068, dilution 1:200, clone D7A5; Cell Signal Technology) (B) ( x 40 magnification). pEGFR were positive at initial diagnosis, which were still present at the time of progression. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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Fluorescence in situ hybridization (FISH) analysis showed MET amplification that had not been observed in initial biopsy specimens (Fig. 2A).