title: CCNA1 promoter methylation: a potential marker for grading Papanicolaou smear cervical squamous intraepithelial lesions.
abstract: BACKGROUND
  From our previous study, we established that cyclin A1 (CCNA1) promoter methylation is strongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as a diagnostic maker of disease.
  
  
  OBJECTIVE
  The purpose of the present study was to assess the prevalence of CCNA1 promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNA screening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters like sensitivity, specificity, predictive values and likelihood ratio.
  
  
  METHODS
  In this retrospective study, histopathology was used as the gold standard method with specimens separated into the following groups: negative (n=31), low- grade squamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse (HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation was examined by CCNA1 duplex methylation specific PCR.
  
  
  RESULTS
  The results showed the frequencies of CCNA1 promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and 100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequency in all three groups, it could not differentiate between the different groups and grades of precancerous lesions. In contrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levels of all statistic parameters.
  
  
  CONCLUSIONS
  CCNA1 promoter methylation is a potential marker for distinguishing between histologic negative/LSIL and HSIL+using cervical cytology samples.
authors.affiliation: Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok ThailandE-mail : Nakarinkit@gmail.com.
authors.forename: Suthipong
authors.initials: S
authors.lastname: Chujan
authors.forename: Nakarin
authors.initials: N
authors.lastname: Kitkumthorn
authors.forename: Sumalee
authors.initials: S
authors.lastname: Siriangkul
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
mesh_terms: D000328:Adult; D056750:Cyclin A1 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D018307:Neoplasms, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000821:virology; D065006:Papanicolaou Test / Q000379:methods*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology* / Q000821:virology
chemical_list: C503745:CCNA1 protein, human; D056750:Cyclin A1