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

Author(s):Show less -

Saggioro, Fabiano P. ^[1] ; Neder, Luciano ^[1] ; Stavale, Joao Norberto ^[2] ; Paixao-Becker, Aline Nazareth P. ^[1] ; Malheiros, Suzana M. F. ^[3] ; Soares, Fernando A. ^[4] ; Pittella, Jose Eymard H. ^[1] ; Matias, Caio Cesar M. S. ^[5] ; Colli, Benedicto O. ^[5] ; Carlotti, Jr., Carlos Gilberto ^[5] ; Franco, Marcello ^[2]

Affiliation

^[1] Univ Sao Paulo FMRR USP, Fac Med Ribeirao Preto, Dept Pathol, Ribeirao Preto, SP - Brazil

^[2] Univ Fed Sao Paulo UNIFESP EPM, Dept Pathol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo UNIFESP EPM, Dept Neurol, Sao Paulo - Brazil

^[4] Hosp Canc AC Camargo, Dept Pathol, Sao Paulo - Brazil

^[5] Univ Sao Paulo FMRP USP, Fac Med Ribeirao Preto, Dept Surg, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: PATHOLOGY RESEARCH AND PRACTICE; v. 210, n. 5, p. 267-273, 2014.
• Web of Science Citations: 20

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. (C) 2014 Elsevier GmbH. All rights reserved. (AU)

• FAPESP's process: 04/09932-4 - Apoptosis in tumors
• Grantee: Marcello Fabiano de Franco
• Support Opportunities: Research Projects - Thematic Grants