gms | German Medical Science

Objective: Clinical protocols combining local chemotherapy with BCNU-wafers and concomitant radiochemotherapy have shown improvement of survival for patients with newly diagnosed malignant glioma. Furthermore molecular genetic data becomes more and more important because of the potential to analyze the biological behaviour and growth potential of gliomas in a clinically helpful manner. Our aim is to determine chromosomal alterations as well as the methylation status of MGMT and p16 (CDKN2A) in order to analyse their influence on survival time, radio- and chemotherapy response.

Method: In our trail 72 patients with histological confirmed glioblastoma were included. Patients will be divided in two treatment groups: group A (36 patients) were treated according the EORTC-Study of Stupp et al. 2005 and group B (36 patients) were treated also according the EORTC-Study and receive additional local chemotherapy with Gliadel. Promoter hypermethylation of the MGMT and p16 (CDKN2A) genes were determined by MS-PCR as described in standard protocols. CGH (comparative genomic hybridisation) analysis will be performed with isolated, labelled DNA of each tumor.

Results: Univariate cox regression showed a prolonged survival time of patients with tumors harboring deletions on chromosome 9p and 10q under chemotherapy treatment (p=0.0042). No significant effect was observed for gains on chromosome 7p. Promotor methylation of the DNA repair protein O₆-methylguanine DNA-methyltransferase (MGMT) in tumor tissue was not associated with prolonged overall survival (p=0.46). Promotor hypermethylation of p16 (CDKN2A) was also not correlated with prolonged overall survival (p=0.821).

Conclusions: Our retrospective study shows no evidence that p16 methylation can act as an additional prognostic marker for survival in patients with glioblastoma treated with alkylating agents. Patients with MGMT promoter methylation had a benefit of chemotherapy whether treated by TMZ or BCNU. In content with recent results MGMT still seems to be an important predictive marker in GBM patients.