title: Meningeal hemangiopericytomas: a clinicopathological study with emphasis on MGMT (O(6) -methylguanine-DNA methyltransferase) promoter methylation status.
abstract: Meningeal hemangiopericytomas (HPCs) are aggressive dural-based tumors, for which no prognostic or predictive marker has been identified. Gross total resection is treatment of choice, but not easily achieved; hence, alkylating agents like temozolomide (TMZ) are now being tried. O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation has proven prognostic and predictive value in glioblastomas. This study evaluates MGMT promoter methylation in meningeal HPCs to determine its role in HPC oncogenesis and its association with patient outcome. Meningeal HPCs diagnosed between 2002 and 2011 were retrieved and clinicopathological features reviewed. MGMT promoter methylation status was assessed by methylation-specific polymerase chain reaction (MSP) and immunohistochemistry (IHC) for MGMT protein. HPCs accounted for 1.1% of all CNS tumors. Forty cases were analyzed; the majority were adults (mean age = 41.4 years). Seventy percent were primary and 30% were recurrent tumors; 60% were grade II and 40% were grade III. MGMT promoter methylation was identified in 45% of cases, including Grade II (54.2%) and Grade III (31.3%) (P = 0.203). Promoter methylation was significantly (P = 0.035) more frequent in primary (57.1%) than in recurrent (16.7%) tumors. No correlation was noted between MGMT promoter methylation by MSP and MGMT protein expression by IHC, or with progression-free survival. Thus, a significant proportion of HPCs demonstrate MGMT promoter methylation, suggesting possible susceptibility to TMZ. As promoter methylation is more frequent in primary tumors, TMZ may serve as a therapeutic option in residual primary tumors. Epigenetic inactivation of MGMT in HPCs necessitates the assessment of prognostic and predictive value of MGMT promoter methylation in HPCs in larger clinical trials.
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Aanchal
authors: A
authors: Kakkar
authors: Anupam
authors: A
authors: Kumar
authors: Prerana
authors: P
authors: Jha
authors: Nishant
authors: N
authors: Goyal
authors: Supriya
authors: S
authors: Mallick
authors: Mehar Chand
authors: MC
authors: Sharma
authors: Ashish
authors: A
authors: Suri
authors: Manmohan
authors: M
authors: Singh
authors: Shashank S
authors: SS
authors: Kale
authors: Pramod Kumar
authors: PK
authors: Julka
authors: Chitra
authors: C
authors: Sarkar
authors: Vaishali
authors: V
authors: Suri
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006393:Hemangiopericytoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: MGMT; Temozolomide; hemangiopericytoma; meningeal tumor; promoter methylation