title: TIMP-2 gene methylation in cervical precursor and invasive lesions.
abstract: OBJECTIVE
  To analyze the presence of HPV-DNA and TIMP-2 gene methylation in cervical precursor and invasive lesions, as well as to study the associations among the latter, the presence of HPV-DNA, and the clinical evolution of such lesions.
  
  
  METHODS
  Cross-sectional study that includes 49 biopsy or brush smear samples from women with a normal cervix, LSIL, HSIL, microinvasive carcinoma and invasive carcinoma. The presence of HPV-DNA and specific methylation was analyzed using PCR. Thirty-eight biopsy samples for HSIL, microinvasive carcinoma and frank invasive carcinoma as well as 11 brush smear samples for LSIL and normal cervices were analyzed.
  
  
  RESULTS
  TIMP-2 gene methylation was detected in 86.8% (33/38) of the samples from the group with lesions and 50% (4/8) of the normal samples (p=0.03). HPV-DNA was detected in 81.6% (31/38) of the samples from the group with lesions and 25% (2/8) of the normal samples (p=0.003). HPV-DNA was more frequent in the methylated samples (50%), and the group with methylation had a higher risk of unfavorable evolution than the group without methylation; however, such observations were not statistically significant (p=0.19).
  
  
  CONCLUSIONS
  TIMP-2 gene methylation and the presence of HPV-DNA were characteristic of the group with cervical lesions. Methylation was not associated with the presence of HPV-DNA or an unfavorable clinical evolution.
authors.affiliation: Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Brazil; Postgraduate Program in Surgical Sciences, Universidade Federal do Rio de Janeiro - UFRJ, Brazil; Institute of Gynecology, Universidade Federal do Rio de Janeiro (UFRJ), Brazil. Electronic address: yarafurtadorj@terra.com.br.
authors.forename: Yara
authors.initials: Y
authors.lastname: Furtado
authors.affiliation: Postgraduate Program in Surgical Sciences, Universidade Federal do Rio de Janeiro - UFRJ, Brazil; Institute of Gynecology, Universidade Federal do Rio de Janeiro (UFRJ), Brazil.
authors.forename: Gutemberg
authors.initials: G
authors.lastname: Almeida
authors.affiliation: Postgraduate Program in Surgical Sciences, Universidade Federal do Rio de Janeiro - UFRJ, Brazil; Institute of Gynecology, Universidade Federal do Rio de Janeiro (UFRJ), Brazil.
authors.forename: Filomena Aste
authors.initials: FA
authors.lastname: Silveira
authors.affiliation: National Institute for Women, Children and Adolescents, Fernandes Figueira Institute, Fundação Oswaldo Cruz (FIOCRUZ), Brazil.
authors.forename: Kátia S
authors.initials: KS
authors.lastname: Silva
authors.affiliation: Institute of Gynecology, Universidade Federal do Rio de Janeiro (UFRJ), Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Maldonado
authors.affiliation: Universidade Federal Fluminense (UFF), Brazil.
authors.forename: Isabel Cristina
authors.initials: IC
authors.lastname: do Val
authors.affiliation: Universidade Federal Fluminense (UFF), Brazil.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cavalcanti
authors.affiliation: Biomedical Sciences Institute, Universidade Federal do Rio de Janeiro (UFRJ), Brazil.
authors.forename: Miranda-Alves
authors.initials: MA
authors.lastname: L
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, Clementino Fraga Filho University Hospital, Universidade Federal do Rio de Janeiro (UFRJ), Brazil.
authors.forename: Maria da Gloria da Costa
authors.initials: Mda G
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D019716:Tissue Inhibitor of Metalloproteinase-2
keywords: Cervix; Methylation; Neoplasia; Papillomavirus infection; TIMP-2