title: Fas, FasL, and cleaved caspases 8 and 3 in glioblastomas: a tissue microarray-based study.
abstract: 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.
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil. Electronic address: fsaggioro@terra.com.br.
authors.forename: Fabiano P
authors.initials: FP
authors.lastname: Saggioro
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.affiliation: Department of Pathology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil.
authors.forename: João Norberto
authors.initials: JN
authors.lastname: Stávale
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Aline Nazareth P
authors.initials: AN
authors.lastname: Paixão-Becker
authors.affiliation: Department of Neurology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil.
authors.forename: Suzana M F
authors.initials: SM
authors.lastname: Malheiros
authors.affiliation: Department of Pathology, Hospital of Cancer A.C. Camargo, São Paulo, SP, Brazil.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: José Eymard H
authors.initials: JE
authors.lastname: Pittella
authors.affiliation: Department of Surgery, Faculty of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Caio César M S
authors.initials: CC
authors.lastname: Matias
authors.affiliation: Department of Surgery, Faculty of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Benedicto O
authors.initials: BO
authors.lastname: Colli
authors.affiliation: Department of Surgery, Faculty of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Carlos Gilberto
authors.initials: CG
authors.lastname: Carlotti
authors.affiliation: Department of Pathology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil.
authors.forename: Marcello
authors.initials: M
authors.lastname: Franco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000627:therapeutic use*; D053181:Caspase 8 / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology; D046888:Tissue Array Analysis / Q000379:methods; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D053181:Caspase 8
keywords: Apoptosis; Caspase 3; Cleaved caspase 8; Glioblastoma; Survival