title: Quantitative assessment of DNA methylation for the detection of cervical and endometrial adenocarcinomas in liquid-based cytology specimens.
abstract: OBJECTIVE
  To investigate the aberrant promoter hypermethylation as a screening tool for cervical adenocarcinomas (CAs) and endometrial adenocarcinomas (EAs) in cervical scrapings.
  
  
  METHODS
  A quantitative multiplex methylation-specific polymerase chain reaction approach was used to examine promoter methylation of 5 genes (APC, HIN-1, RAR-beta, RASSF1A and Twist) in biopsy-confirmed CA (n = 31) and EA (n = 27) residual, liquid-based cytology samples. The data of negative for intraepithelial lesions or malignancy and low-grade squamous intraepithelial lesions were used as controls.
  
  
  RESULTS
  Methylation levels of APC, RAR-beta, RASSF1A and Twist were significantly higher in CA than in control cervical samples. For EA, only the methylation levels of RASSF1A differed significantly from those of control. Receiver-operating characteristic analysis demonstrated that APC, RAR-beta and RASSF1A had the ability to distinguish CA/EA, CA and EA from control samples. In CA/EA and CA samples, the best 3-gene combination was RASSF1A/RAR-beta/APC. This 3-gene panel had a sensitivity of 87.0% for CA/EA and of 80.6% for CA and a specificity of 79.3% for both CA/EA and CA. In EA samples, RASSF1A showed the best performance in distinguishing EA from control. The estimated sensitivity of RASSF1A for detecting EA was 63.0%, and its specificity was 96.3%.
  
  
  CONCLUSIONS
  This feasibility study demonstrates that quantitative detection of aberrant DNA methylation in cervical scrapings may be a promising new diagnostic tool for the detection of CA and EA.
authors.affiliation: Department of Pathology, Seonam University, College of Medicine, Namwon, Republic of Korea.
authors.forename: Ga-Eon
authors.initials: GE
authors.lastname: Kim
authors.forename: Sun-Seog
authors.initials: SS
authors.lastname: Kweon
authors.forename: Ji Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Nam
authors.forename: Chan
authors.initials: C
authors.lastname: Choi
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D003581:Cytodiagnosis / Q000379:methods; D003584:Cytological Techniques; D019175:DNA Methylation / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D012372:ROC Curve; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta