title: High PCNA index in meningiomas resistant to radiation therapy.
abstract: OBJECTIVE
  Meningiomas are common intracranial tumors, often well controlled with surgical resection alone. While the efficacy of radiation therapy in improving local control and progression-free survival is well documented, prognostic data substantiate factors that are predictive of poor local control following definitive radiation therapy. PCNA is a DNA polymerase expressed at the highest levels in the S-phase, the most resistant portion of the cell cycle to ionizing radiation in vitro. We investigated the possible correlation between the levels of PCNA expression and the clinical outcome of patients treated with definitive radiation therapy.
  
  
  METHODS
  Archival tissue was collected from 33 cases of meningioma treated at our institution for definitive radiation therapy between 1970 and 1990. Age-matched normal meningeal tissue and asymptomatic meningiomas removed at autopsy served as tissue controls. A standard ABC immumoperoxidase technique employing antibodies to PCNA, PC-10 (Dako, California) was used to stain specimen slides for PCNA. PCNA index was defined as the number of positive nuclei per 10 high-power fields at 400x magnification. Two independent observers scored the slides without prior knowledge of the cases at hand.
  
  
  RESULTS
  Patients with high PCNA index were less likely to be controlled by therapeutic radiation (p < 0.001, Kaplan-Meier). All patients with a PCNA index greater that 25 failed radiation therapy. Using multivariate analyses, malignant (but not atypical), histology and PCNA index were significant predictors of progression following radiation therapy (p < 0.05, log rank).
  
  
  CONCLUSIONS
  PCNA index may be a useful adjunct to more standard histopathologic criteria in the determination of meningioma local control and progression-free survival following therapeutic irradiation. Data on a more expanded population evaluated on a prospective basis will be needed before such criteria are routinely employed in the clinical setting.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: K T
authors.initials: KT
authors.lastname: Colvett
authors.forename: D W
authors.initials: DW
authors.lastname: Hsu
authors.forename: M
authors.initials: M
authors.lastname: Su
authors.forename: R M
authors.initials: RM
authors.lastname: Lingood
authors.forename: F S
authors.initials: FS
authors.lastname: Pardo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D008579:Meningioma / Q000378:metabolism* / Q000532:radiotherapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D017211:Treatment Failure
chemical_list: D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen