title: Protein expression of Fas, Fas ligand, Bcl-2 and TGFbeta2 and correlation with survival in initial and recurrent human gliomas.
abstract: Several studies have recently demonstrated that human gliomas express Fas, Fas ligand (FasL), Bcl-2 and TGFbeta2 at some degree. These factors are considered to interact with apoptotic processes and to have immuno-reactive potential. Their role for tumor evasion from the immune surveillance is currently under examination. To date, there is only limited information about the definite expression patterns of these four factors in human gliomas, particularly in pilocytic astrocytoma (PA) and recurrent tumors. We analyzed 75 human gliomas for the immunohistochemical expression of Fas, FasL, Bcl-2, and TGFbeta2: (1) 25 PAs (WHO grade I), (2) 25 primary glioblastomas (WHO grade IV), and (3) 25 paired initial and recurrent glioblastomas (WHO grade IV), respectively. Co-expression of all four factors was present in the majority of specimens, i.e. in 72% (18/25) of PAs and 88% (47/50) of primary glioblastomas. Pilocytic astrocytomas showed significantly higher scores of TGFbeta2 expression (p < 0.05) and significantly lower Fas, Fas ligand and Bcl-2 scores (p < 0.05) than glioblastomas. There were no significant expression differences in initial versus recurrent glioblastoma specimens. Likewise, no significant correlation was observed between protein expression and clinical parameters, i.e. total survival time or progression free survival time, as documented by Kaplan-Meier method and log rank-test. In conclusion, Fas, FasL, Bcl-2 and TGFbeta2 are differently expressed in PAs versus glioblastomas. These factors, however, are not associated with patient prognosis. The broad co-expression of these factors may enable new therapeutic approaches in the future.
authors.affiliation: Department of Neurosurgery, University Hospital Kiel, Germany. rainer_strege@gmx.de
authors.forename: Rainer J
authors.initials: RJ
authors.lastname: Strege
authors.forename: Christian
authors.initials: C
authors.lastname: Godt
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Stark
authors.forename: Heinz-Hermann
authors.initials: HH
authors.lastname: Hugo
authors.forename: H Maximilian
authors.initials: HM
authors.lastname: Mehdorn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053781:Transforming Growth Factor beta2; D019014:fas Receptor / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D019014:fas Receptor