title: Pathodiagnostic parameters and evaluation of O⁶- methyl guanine methyl transferase gene promoter methylation in meningiomas.
abstract: Histopathological evaluation and grading of meningioma give important prognostic information. We evaluated retrospectively monotonous sheeting, necrosis, hypercellularity, nuclear pleomorphism, small cell changes, brain invasion, mitosis, mast cells, psammoma bodies, MIB-1 labeling index (MIB-1 LI) and histological grade of 230 primary meningioma tumors according to the latest World Health Organization (WHO) classification. To reveal any possible association between clinical features and promoter hypermethylation of O(6)-methylguanine-DNA methyltransferase (MGMT) as an important epigenetic modification in many human cancers, we also evaluated the methylation status of MGMT in meningiomas by a SYBR-green-based real-time PCR method. There was a female predominance (2.38 to 1) in the meningiomas. The mean age of the patients was 49.9 ± 12.6 years (range 16 to 78 years). Transitional meningiomas were the most common subtype of the meningiomas (35.21%, n=81). Most of the meningiomas were located in the falx and parasagital area. There was a significant correlation between histopathological features of malignancy. These features were observed more frequently and with statistical relation to grade II rather than grade I. Mast cells, psammoma bodies and nuclear pleomorphism had poor associations (P>0.05). When we re-evaluated the tumor grading, 31 patients with grade I meningiomas were upgraded to grade II. None of the meningiomas tested by MSQP were methylated in MGMT promoter sequence. High MIB-1 LI could be indicative for higher grade of meningioma. Continuous revision of the classification system is needed to improve the accuracy of prognostic judgments in meningioma. The data confirm that there is no rationale to test meningiomas for MGMT methylation status.
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran. Electronic address: jabinir861@mums.ac.ir.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Jabini
authors.affiliation: Cancer Research Center, Shohada Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1931746345, Iran. Electronic address: afshinmo2002@yahoo.com.
authors.forename: Afshin
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Department of Biochemistry, Mashhad Branch, Islamic Azad University of Mashhad, Mashhad 91735/413, Iran. Electronic address: sanegad@yahoo.com.
authors.forename: Sima
authors.initials: S
authors.lastname: Afsharnezhad
authors.affiliation: Cancer Molecular Pathology Research Center, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad 91766-99199, Iran. Electronic address: ayatollahih@mums.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Ayatollahi
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran. Electronic address: behravanj@mums.ac.ir.
authors.forename: Javad
authors.initials: J
authors.lastname: Behravan
authors.affiliation: Department of Radiation Oncology, University of Toronto, Toronto M2N0C8, Canada. Electronic address: hamidreza.raziee@utoronto.ca.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Raziee
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran. Electronic address: mosaffaf@mums.ac.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D008579:Meningioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: Hypermethylation; MGMT; Meningioma; Pathology; Real-time PCR; Tumor grading