Fas, FasL, and cleaved caspases 8 and 3 in glioblastomas: A tissue microarray-based study

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Saggioro, Fabiano Pinto
Neder, Luciano
Stávale, João Norberto [UNIFESP]
Paixão-Becker, Aline Nazareth de Paiva
Malheiros, Suzana Maria Fleury [UNIFESP]
Soares, Fernando Augusto
Pittella, José Eymard Homem
Matias, Caio César Marconato Simões
Colli, Benedicto Oscar
Carlotti Junior, Carlos Gilberto
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This investigation analyzed the immunoexpression of FasL, Fas, cleaved caspase-8, and cleaved caspase-3 in glioblastomas. Formalin-fixed and paraffin-embedded glioblastoma tissues and control brain tissues from 97 patients were analyzed by tissue microarrays and immunohistochemistry. Patients with glioblastomas that were negative or weakly stained (<50% of cells positive) for cleaved caspase-8 had worse cancer-specific overall survival (median=8.5 months) than did patients with tumors that highly expressed cleaved caspase-8 (median=11.7 months; P=0.0325), independent of clinical variables. There was no association of other markers with survival, treatment, sex, age, tumor size, and primary site. Among the tumors, there were reasonable to good positive correlations between the expression of FasL and Fas (r=0.47) and between Fas and cleaved caspase-8 (r=0.41), and there were poor positive correlations between Fas and cleaved caspase-3 (r=0.26), FasL and cleaved caspase-8 (r=0.22), and cleaved caspase-8 and -3 (r=0.31). Our results suggest that Fas-Fas-ligand signal transduction could be inhibited, especially at the stage of caspase-8 activation, thereby establishing a major mechanism for evasion of apoptosis by these tumors. the absence or low expression of cleaved caspase-8 in the tumors was a negative prognostic indicator for patient survival. (C) 2014 Elsevier GmbH. All rights reserved.
Pathology Research and Practice. Jena: Elsevier Gmbh, Urban & Fischer Verlag, v. 210, n. 5, p. 267-273, 2014.