title: Correlation of tumor p53 and PCNA with response and survival of glioblastoma in patients treated with an ECOG protocol of pre-irradiation chemotherapy.
abstract: BACKGROUND
  The ability to predict treatment responsiveness and survival of patients with glioblastoma multiforme, the most malignant and most common primary brain tumor, would be a valuable asset. Tumor and proliferation markers such as p53 and PCNA have been immunohistochemically defined and have been useful in other tumors in determining prognosis. Therefore, the authors studied the correlation of responsiveness to treatment, time to progression and survival with p53 and PCNA labeling indices in a pre-irradiation chemotherapy study of the glioblastoma multiforme.
  
  
  METHODS
  Immunohistopathology for labeling indices for p53 and PCNA using formalin-fixed, paraffin-embedded tissue from the glioblastomas of 23 patients entered into a phase II ECOG trial of pre-irradiation chemotherapy were defined using the streptavidin-peroxidase technique with AEC chromogen. The labeling indices were correlated with response to treatment time to progression and overall survival. Most patients received three cycles of BCNU for three days over three months and cisplatin monthly for three days over three months prior to external beam irradiation.
  
  
  RESULTS
  There were no significant differences in treatment response, time to progression or overall survival in glioblastoma, patients with positive p53 labeling index (> 5%) versus a negative p53 labeling index (< or = 5%) or positive PCNA labeling (> 10%) versus a negative labeling index (< or = 10%) or any combination of P53 and PCNA labeling indices.
  
  
  CONCLUSIONS
  Using this protocol of pre-irradiation chemotherapy, p53 and PCNA labeling indices in the glioblastoma multiforme did not predict treatment benefit.
authors.affiliation: Department of Pathology, University of Connecticut Health Center, Farmington 06032, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Grunnet
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.forename: M
authors.initials: M
authors.lastname: Gilbert
authors.forename: R
authors.initials: R
authors.lastname: Hellman
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D011878:Radiotherapy; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53