title: Triage of Atypical Glandular Cell by SOX1 and POU4F3 Methylation: A Taiwanese Gynecologic Oncology Group (TGOG) Study.
abstract: BACKGROUND
  Invasive procedures including loop electrosurgical excision, cervical conization, and endometrial sampling are often recommended when atypical glandular cells (AGC) are detected on Pap smear with unsatisfactory colposcopy. These invasive procedures may result in patient anxiety, increased medical expense, and increasing the risk of preterm delivery in subsequent pregnancies. This study was performed to assess methylation biomarkers in the triage of AGC on Pap smear for invasive procedures.
  
  
  METHODS
  We conducted a multicenter study in 13 medical centers in Taiwan from May 2012 to May 2014. A total of 55 samples diagnosed "AGC not otherwise specified" (AGC-NOS) were included. All patients with AGC underwent colposcopy, cervical biopsy, endometrial sampling, and conization if indicated. Multiplex quantitative methylation-specific polymerase chain reaction (QMSPCR) was performed. Sensitivity, specificity, and accuracy were calculated for detecting CIN3+ and endometrial complex hyperplasia.
  
  
  RESULTS
  In 55 patients with AGC, the sensitivity for methylated (m) SOX1m, PAX1 m, ZNF582m,PTPRRm, AJAP1m, HS3ST2m, and POU4F3m for detecting CIN3+ and endometrial complex hyperplasia lesions was 100, 86, 71, 86, 86, 57, and 100%; specificity was 67, 79, 85, 50, 52, 96, and 52%, respectively. Testing for high risk-HPV had a sensitivity of 57% and specificity of 75% for CIN3+ and endometrial complex hyperplasia lesions.
  
  
  CONCLUSIONS
  Methylated (m) SOX1m and POU4F3m could be new methylation biomarkers for detection of CIN3+ and endometrial complex hyperplasia in AGC. Women with AGC and positive SOX1m / POU4F3m, colposcopy, cervical conization or endometrial sampling should be considered.
authors.affiliation: Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Cheng-Chang
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C.
authors.forename: Yu-Che
authors.initials: YC
authors.lastname: Ou
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Kung-Liahng
authors.initials: KL
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, Taiwan, R.O.C.
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Chi-Hau
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, R.O.C.
authors.forename: Tang-Yuan
authors.initials: TY
authors.lastname: Chu
authors.affiliation: Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Shih-Tien
authors.initials: ST
authors.lastname: Hsu
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Wen-Shiung
authors.initials: WS
authors.lastname: Liou
authors.affiliation: Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Yin-Yi
authors.initials: YY
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Hua-Hsi
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
authors.forename: Tze-Ho
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C; Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, R.O.C; Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
authors.forename: Hung-Cheng
authors.initials: HC
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D013624:Taiwan; D050821:Transcription Factor Brn-3C / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C111223:POU4F3 protein, human; C490906:SOX1 protein, human; D055748:SOXB1 Transcription Factors; D050821:Transcription Factor Brn-3C