title: CDKN2A promoter hypermethylation in astrocytomas is associated with age and sex.
abstract: CDKN2A promoter hypermethylation has been widely related to many cancers. In astrocytomas, although CDKN2A (p16(INK4A) protein) is often inactivated, there are still some controversial issues regarding the mechanism by which this alteration occurs. Thus, we analyzed a series of astrocytomas to assess the association between CDKN2A expression and methylation of grade I-IV tumors (WHO) and clinicopathological parameters. DNA extracted from formalin-fixed paraffin-embedded material of 93 astrocytic tumors was available for CDKN2A promoter methylation analysis and p16(INK4A) expression by methylation-specific PCR and immunohistochemistry, respectively. A strong negative correlation between nuclear and cytoplasmic immunostaining and CDKN2A promoter methylation was found. Additionally, a significant negative correlation between CDKN2A promoter methylation and age was observed; also, female patients had statistically more CDKN2A methylated promoters (p = 0.036) than men. In conclusion, CDKN2A inactivation by promoter methylation is a frequent event in astrocytomas and it is related to the age and sex of patients.
authors.affiliation: Universidade Federal do Ceará, Department of Pathology and Forensic Medicine, Rua Alexandre Baraúna, 949, Porangabussu, CEP 60183-630 Fortaleza, Brazil. markenialves@yahoo.com.br
authors.forename: Markênia Kélia Santos
authors.initials: MK
authors.lastname: Alves
authors.forename: Mário Henrique Girão
authors.initials: MH
authors.lastname: Faria
authors.forename: Eduardo Henrique Cunha
authors.initials: EH
authors.lastname: Neves Filho
authors.forename: Adriana Camargo
authors.initials: AC
authors.lastname: Ferrasi
authors.forename: Maria Inês de Moura Campos
authors.initials: MI
authors.lastname: Pardini
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Moraes Filho
authors.forename: Silvia Helena Barem
authors.initials: SH
authors.lastname: Rabenhorst
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D018709:Statistics, Nonparametric
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Age; Astrocytic tumors; CDKN2A Methylation; Expression; p16