gms | German Medical Science

Objective: Hemangiopericytomas of the central nervous system are often characterized by aggressive biological behavior and recurrent tumor growth. Hypermethylation of the MGMT (O₆-methylguanine-DNA methyltransferase) promoter is an important prognostic marker and also predicts response to therapy with alkylating agents (e.g. temozolomide) in patients with malignant gliomas. In hemangiopericytomas, a prognostic effect of MGMT protein expression status has been reported, but data on MGMT promoter methylation are lacking. Because temozolomide has been shown to be well-tolerated and beneficial in the treatment of hemangiopericytomas, we aimed to examine, if MGMT promoter status could be used as a potential prognostic or predictive marker.

Method: Formalin-fixed paraffin-embedded tissue samples from hemangiopericytomas of the central nervous system diagnosed from 1988 to 2009 were retrieved from the archives of the Institute of Neuropathology Münster and the Institute of Pathology and Neuropathology Essen. All samples were reviewed neuropathologically according to current WHO criteria. After isolation and bisulifite conversion (EZ DNA Methylation-Gold Kit, Zymo Research, Orange, CA), DNA from representative tumor material was subjected to methylation-specific PCR as described previously.

Results: Using the above approach, a total of 54 samples from 43 patients could be examined. The median age of the 19 females and 24 males was 54 years (range: 23-85 years). Twenty-nine of the primary tumors were graded as WHO grade II, while 14 tumors were WHO grade III. Sixty-seven percent of the hemangiopericytomas were of supratentorial location. After methylation-specific PCR, MGMT promoter methylation status was negative in all cases. Using the same methodology, MGMT promoter methylation status was positive in 384 out of 822 malignant astrocytic tumors (47%, data not shown).

Conclusions: The absence of MGMT promoter methylation in all primary and recurrent samples in this large representative series of central nervous system hemangiopericytomas clearly argues against the use of MGMT promoter methylation status as a prognostic or predictive marker. It seems also unlikely that MGMT protein expression might be related to MGMT promoter methylation. Even though the role of alkylating agents in the treatment of hemangiopericytomas remains to be further elucidated, our data provide no rationale for the determination of MGMT methylation status in this context.