title: Survivin in glioblastomas. Protein and messenger RNA expression and comparison with telomerase levels.
abstract: BACKGROUND
  Survivin is a novel inhibitor of apoptosis that acts via a pathway independent of bcl-2. Little is known about its distribution in brain tumors or how it correlates with other biomarkers of malignancy, such as telomerase, an enzyme that plays a critical role in cellular immortalization and cancer biology.
  
  
  OBJECTIVE
  To assess survivin protein expression in gliomas and to compare expression with that of telomerase.
  
  
  METHODS
  Immunohistochemical staining for survivin protein expression was performed using an antibody developed in our laboratory. Quantitative survivin messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction. In selected cases, survivin results were compared with quantitative telomerase values analyzed by polymerase chain reaction-based telomerase repeat amplification protocol (TRAP) assay. Twenty-five tumor tissue samples from 16 cases of glioblastoma multiforme (GBM; including multiple tissue samples in 6 patients), 2 grade II gliomas, 4 grade III gliomas, and 3 control temporal lobectomy specimens were studied.
  
  
  RESULTS
  Nuclear immunoreactivity for survivin protein and survivin mRNA were detectable in most glioma samples, regardless of grade. Glioblastoma multiforme demonstrated moderate protein expression and survivin mRNA levels compared to epithelial malignancies previously tested in our laboratory. Although the association of survivin mRNA with the levels of telomerase within the GBM cases did not reach statistical significance, most GBMs also expressed survivin. The quantitative score for survivin mRNA was higher in GBMs than in grade II and III gliomas (P =.02), after accounting for multiple specimens per patient.
  
  
  CONCLUSIONS
  Quantitative survivin mRNA analysis, but not immunohistochemistry, distinguished GBMs from lower grade gliomas. Mechanisms that promote both cell proliferation (telomerase expression) and cell survival (survivin expression) are often activated in GBMs.
authors.affiliation: Department of Pathology, University of Colorado Health Sciences Center, Denver, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
authors.forename: David
authors.initials: D
authors.lastname: Heinz
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McCarthy
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Bobak
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Lillehei
authors.forename: A Laurie W
authors.initials: AL
authors.lastname: Shroyer
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Shroyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D005260:Female; D005909:Glioblastoma / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; D019098:Telomerase