title: Molecular biomarkers in endometrial hyperplasias predict cancer progression.
abstract: OBJECTIVE
  The purpose of this study was to assess the value of the 2003 World Health Organization (WHO) and endometrial intraepithelial neoplasia (EIN) classifications, D-score, and molecular biomarkers in endometrial hyperplasia (EH) for cancer progression.
  
  
  METHODS
  We conducted a review of 307 endometrial hyperplasias for WHO and EIN classifications and an analysis of biomarkers, D-score, and cancer progression-free survival.
  
  
  RESULTS
  The WHO, EIN, D-score, and many biomarkers were prognostic; 7.2% of the samples progressed to cancer. The WHO and EIN classifications correlated weakly with CK5/6 and p16. The D-score was strongest prognostically. When >1, it had the lowest false-negative progression rate of all features analyzed. COX2 negativity was the only other independent multivariate cancer progression predictor in endometrial hyperplasia, but only in cases with D-score <1. Eight of 13 cases (61%), with a combined D-score of <1 and negative COX2 progressed, which contrasted with 3 of 139 of all other cases (2.8%) (P < .0001; hazard ratio, 53.0). The biomarkers did not strengthen the prognostic value of the WHO or EIN classification.
  
  
  CONCLUSIONS
  Combined D-score <1 and COX2 negativity strongly predict cancer progression in endometrial hyperplasias.
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Anita
authors.initials: A
authors.lastname: Steinbakk
authors.forename: Einar
authors.initials: E
authors.lastname: Gudlaugsson
authors.forename: Ole Gunnar
authors.initials: OG
authors.lastname: Aasprong
authors.forename: Ivar
authors.initials: I
authors.lastname: Skaland
authors.forename: Anais
authors.initials: A
authors.lastname: Malpica
authors.forename: Weiwei
authors.initials: W
authors.lastname: Feng
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.forename: Jan P
authors.initials: JP
authors.lastname: Baak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002278:Carcinoma in Situ / Q000145:classification / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051546:Cyclooxygenase 2 / Q000032:analysis; D004714:Endometrial Hyperplasia / Q000145:classification / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000145:classification / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000032:analysis; D053553:Keratin-6 / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D011379:Prognosis; D014944:World Health Organization
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D053555:Keratin-5; D053553:Keratin-6; D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human