BACKGROUND: In Ewing sarcoma (EWS) most of the research on signaling pathways has been performed on cell lines or animal models. The objective of the current study was to determine the relation between clinical outcome and the expression of proteins involved in active growth signaling pathways. METHODS: A paraffin-embedded microarray of 45 human primary EWS tissue specimens was stained with the antibodies against c-KIT, AKT, p-AKT, p-mTOR, IGF-1R, IGFBP-3, MAPK, p27(KIP1) , and p70S6 kinase. Immunohistochemical staining was correlated with patient overall survival (OS). RESULTS: In the univariate analysis 3 variables showed statistical significance to predict survival: presence of metastasis, p-mTOR, and p27(KIP1). A positive stain for p-mTOR (hazard ratio of 4.74 [95% CI (57, 121)]) was significantly (log-rank test with a P = 0.029) associated with better OS. Also, a positive stain for p27(KIP1) (hazard ratio of 6.87 [95% CI (77, 136)] was significantly (log-rank test with a P = 0.009) associated with better OS. Multivariate analysis showed metastasis (HR: 4.3; 95% CI: 0.99, 19; P = 0.05), p-mTOR (HR: 4.8 with 95% CI: 0.6, 38; P = 0.13) and p27 (HR: 5.3; 95% CI: 1.37, 20; P = 0.01) as independent prognostic factors of outcome. CONCLUSIONS: In our series, p-mTOR and p27(KIP1) protein overexpression were independently associated with better survival.
BACKGROUND: In Ewing sarcoma (EWS) most of the research on signaling pathways has been performed on cell lines or animal models. The objective of the current study was to determine the relation between clinical outcome and the expression of proteins involved in active growth signaling pathways. METHODS: A paraffin-embedded microarray of 45 human primary EWS tissue specimens was stained with the antibodies against c-KIT, AKT, p-AKT, p-mTOR, IGF-1R, IGFBP-3, MAPK, p27(KIP1) , and p70S6 kinase. Immunohistochemical staining was correlated with patient overall survival (OS). RESULTS: In the univariate analysis 3 variables showed statistical significance to predict survival: presence of metastasis, p-mTOR, and p27(KIP1). A positive stain for p-mTOR (hazard ratio of 4.74 [95% CI (57, 121)]) was significantly (log-rank test with a P = 0.029) associated with better OS. Also, a positive stain for p27(KIP1) (hazard ratio of 6.87 [95% CI (77, 136)] was significantly (log-rank test with a P = 0.009) associated with better OS. Multivariate analysis showed metastasis (HR: 4.3; 95% CI: 0.99, 19; P = 0.05), p-mTOR (HR: 4.8 with 95% CI: 0.6, 38; P = 0.13) and p27 (HR: 5.3; 95% CI: 1.37, 20; P = 0.01) as independent prognostic factors of outcome. CONCLUSIONS: In our series, p-mTOR and p27(KIP1) protein overexpression were independently associated with better survival.
Authors: A C M van de Luijtgaarden; Y M H Versleijen-Jonkers; M H S Roeffen; H W B Schreuder; U E Flucke; W T A van der Graaf Journal: Target Oncol Date: 2013-01-06 Impact factor: 4.493
Authors: Lara Grande; Gabriel Bretones; Manuel Rosa-Garrido; Eva M Garrido-Martin; Teresa Hernandez; Susana Fraile; Luisa Botella; Enrique de Alava; August Vidal; Xavier Garcia del Muro; Alberto Villanueva; M Dolores Delgado; Jose L Fernandez-Luna Journal: J Biol Chem Date: 2012-06-20 Impact factor: 5.157
Authors: Yongqing Liu; Ester Sánchez-Tilló; Xiaoqin Lu; Li Huang; Brian Clem; Sucheta Telang; Alfred B Jenson; Miriam Cuatrecasas; Jason Chesney; Antonio Postigo; Douglas C Dean Journal: J Biol Chem Date: 2013-02-26 Impact factor: 5.157
Authors: Mark A Applebaum; Dafydd G Thomas; Todd Hembrough; Jon Burrows; Andrew E Horvai; Elizabeth R Lawlor; Steven G DuBois Journal: Appl Immunohistochem Mol Morphol Date: 2014-09
Authors: Laura Lagares-Tena; Silvia García-Monclús; Roser López-Alemany; Olga Almacellas-Rabaiget; Juan Huertas-Martínez; Miguel Sáinz-Jaspeado; Silvia Mateo-Lozano; Carlos Rodríguez-Galindo; Santiago Rello-Varona; David Herrero-Martín; Oscar M Tirado Journal: Oncotarget Date: 2016-08-30