gms | German Medical Science

Objective: Promoter methylation of P15, P16, RB1, and MGMT displays an impact on the prognosis of many glioma subtypes. The question arises whether promoter methylation of these genes also has an impact on the clinical course of pilocytic astrocytomas.

Methods: Using methylation-specific polymerase chain reaction, the methylation status of the tumor suppressor genes P15, P16, RB1, and MGMT in pilocytic astrocytomas (n = 18) were analyzed. Immunohistochemical staining for the R132H mutation of the IDH1 gene was performed. Clinical data such as age, gender, localization of the tumor, extent of resection, treatment modality, progression-free survival, and overall survival were scrutinized.

Results: The methylation index for P15, P16, RB1, and MGMT was 0.0%, 0.0%, 5.6% (1/18), and 44.5% (8/18), respectively. If the MGMT promoter was methylated, the probability of relapse and second subsequent therapy was significantly higher (p = 0.019). The one patient with methylation of P15 displayed a poor clinical course. The pilocytic astrocytomas of all 18 patients showed wild-type IDH1. Clinically, there was a significant correlation of subtotal resection with the occurrence of relapse (p = 0.005) and of the localization of the tumor with the extent of resection (p = 0.031). Gross total resection was achieved significantly more often in pediatric patients than in adult patients (p = 0.003). Adult patients showed more relapses after the first tumor resection (p = 0.001).

Conclusion: This study indicates that methylation of MGMT is associated with a worse clinical course and represents an age-independent risk factor for an unfavorable outcome. Other influential factors on outcome were the age of the patient and extent of resection.