Correlation of tumor p53 and PCNA with response and survival of glioblastoma in patients treated with an ECOG protocol of pre-irradiation chemotherapy

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 mar kers such as p53 and PCNA have been immunohistochemically defined and have been useful in other tumors in determining prognosis. Therefore, the author s studied the correlation of responsiveness to treatment, time to progressi on and survival with p53 and PCNA labeling indices in a pre-irradiation che motherapy study of the glioblastoma multiforme. Methods: Immunohistopatholo gy for labeling indices for p53 and PCNA using formalin-fixed, paraffin-emb edded tissue from the glioblastomas of 23 patients entered into a phase II ECOG trial of pre-irradiation chemotherapy were defined using the streptavi din-peroxidase technique with AEC chromogen. The labeling indices were corr elated with response to treatment time to progression and overall survival. Most patients received three cycles of BCNU for three days over three mont hs and cisplatin monthly for three days over three months prior to external beam irradiation. Results: There were no significant differences in treatm ent response, time to progression or overall survival in glioblastoma, pati ents with positive p53 labeling index (>5%) versus a negative p53 labeling index (less than or equal to 5%) or positive PCNA labeling(>10%) versus a n egative labeling index (less than or equal to 10%) or any combination of P5 3 and PCNA labeling indices. Conclusions: Using this protocol of pre-irradi ation chemotherapy, p53 and PCNA labeling indices in the glioblastoma multi forme did not predict treatment benefit.