title: Prognostic significance of the immunohistochemical staining of cleaved caspase-3, an activated form of caspase-3, in gliomas.
abstract: OBJECTIVE
  Gliomas are common tumors of the central nervous system, and the majority of patients with gliomas have a poor prognosis. The prediction of prognosis is very important in selecting treatment. In the present study, we retrospectively examined the immunohistochemical staining of cleaved caspase-3 (CC3), an activated form of caspase-3 that acts as a lethal protease at the most distal stage of the apoptosis pathway, in gliomas, and the correlation between the prognosis of patients and caspase-3 activation to find useful prognostic indicators.
  
  
  METHODS
  Immunohistochemical staining of CC3 was done in 65 patients with gliomas. The percentage of CC3 staining-positive cells was defined as the CC3 immunoreactivity score (IRS). Survival analysis between CC3 IRS of glioma patients and survival time was carried out using the Kaplan-Meier method with the log-rank test and the Cox proportional hazards regression model.
  
  
  RESULTS
  CC3 IRS was statistically analyzed to designate the best provisional cutoff point, and when detected in >10% of glioma cells, it was considered positive. The Kaplan-Meier method with the log-rank test revealed that patients with CC3 IRS-positive tumors had significantly greater survival than those with CC3 IRS-negative tumors among three grades, 2, 3, and 4 (P = 0.0061), and within grade 3 of anaplastic astrocytoma (P = 0.0458). After adjustment for known clinical prognostic factors, such as age, WHO grade, and performance status, the hazard ratio for CC3 IRS-positive was 0.39 with 95% confidence interval between 0.19 and 0.85 (P = 0.0187). Within high grades, including grades 3 and 4, the hazard ratio was 0.40 with 95% confidence interval between 0.20 and 0.86 (P = 0.0192).
  
  
  CONCLUSIONS
  CC3 IRS could be useful as a good prognostic indicator for glioma patients.
authors.affiliation: Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nomiyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hongo
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D053148:Caspase 3