title: The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system.
abstract: BACKGROUND
  The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias.
  
  
  METHODS
  A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had < 1 year of follow-up.
  
  
  RESULTS
  Twenty-four of 477 hyperplasias (5.0%) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354 nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3% in simple hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias, and 38% in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with < 1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively).
  
  
  CONCLUSIONS
  The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway. baja@sir.no
authors.forename: Jan P
authors.initials: JP
authors.lastname: Baak
authors.forename: George L
authors.initials: GL
authors.lastname: Mutter
authors.forename: Stanley
authors.initials: S
authors.lastname: Robboy
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Anne M
authors.initials: AM
authors.lastname: Uyterlinde
authors.forename: Anne
authors.initials: A
authors.lastname: Orbo
authors.forename: Juan
authors.initials: J
authors.lastname: Palazzo
authors.forename: Bent
authors.initials: B
authors.lastname: Fiane
authors.forename: Kjell
authors.initials: K
authors.lastname: Løvslett
authors.forename: Curt
authors.initials: C
authors.lastname: Burger
authors.forename: Feja
authors.initials: F
authors.lastname: Voorhorst
authors.forename: René H
authors.initials: RH
authors.lastname: Verheijen
mesh_terms: D000328:Adult; D000368:Aged; D001837:Body Weights and Measures; D002278:Carcinoma in Situ / Q000145:classification*; D018450:Disease Progression; D004714:Endometrial Hyperplasia / Q000503:physiopathology*; D016889:Endometrial Neoplasms / Q000145:classification*; D005260:Female; D006801:Humans; D008875:Middle Aged; D008967:Molecular Biology; D011379:Prognosis; D012680:Sensitivity and Specificity; D014944:World Health Organization