Expression and clinical relevance of MET and ALK in Ewing sarcomas

摘要: Because novel therapeutic options are limited in Ewing sarcomas (ES), we investigated the expression, genetic aberrations and clinical relevance of MET anaplastic lymphoma kinase (ALK) ES determined targeting these receptors. ALK protein expression was immunohistochemically 31 (50 samples) 36 (59 patients, respectively. Samples included primary tumors, postchemotherapy resections, metastases relapses. RTK domains were sequenced respectively 33 32 tumors. Five cell lines treated vitro with MET/ALK-inhibitor crizotinib, ALK-inhibitor NVP-TAE684 or MET-inhibitor cabozantinib analyzed by MTT assays. Modest to high detected majority (86 69%, respectively). significantly lower resections compared paired untreated tumors (p = 0.031, z -2.310, n 11). In (n 20), membranous correlated a poor overall survival (OS) (60 vs. 197 months, p 0.014). There trend toward event-free (67 111 0.078) OS (88 128 0.074) patients highest levels 29). domain demonstrated 5/32 (16%) 3/33 (9%) Crizotinib (IC50 1.22-3.59 μmol/L), 0.15-0.79 μmol/L) 2.69-8.27 affected viability vitro. Altogether, our data suggest that potential targets receptors may be great interest rationally design future studies ES.