title: Prognostic markers for coexistent carcinoma in high-risk endometrial hyperplasia with negative D-score: significance of morphometry, hormone receptors and apoptosis for outcome prediction.
abstract: OBJECTIVE
  Hysterectomy represents the current routine therapy for high-risk endometrial precancers. More sophisticated methods are needed for treatment decision among women who want to preserve fertility and seriously ill patients. Among women diagnosed with high-risk hyperplasia, approximately 40% show signs of endometrial cancer in the hysterectomy specimen. Thus, more sophisticated methods are needed to select the women at risk.
  
  
  METHODS
  University Hospital of Tromsø, Regional Center for Gynecological Oncology in northern Norway.
  
  
  METHODS
  From 1999 to 2004, 258 consecutive patients had endometrial hyperplasia diagnosed by D-score; 57 among these were high-risk cases (D-score < 0) and 10 had coexisting endometrial carcinoma. No further cancers were detected after long-term follow-up (4-10 years).
  
  
  METHODS
  From the initial histological specimens, material from the 10 patients with cancer and from the 13 cases without cancer (high-risk D-score < 0) was analyzed with selected histomorphometric (architectural and nuclear) and immunohistochemical (hormone receptors and apoptotic) features blinded to the investigator.
  
  
  METHODS
  Original slides were used for computerized histomorphometry (4-class rule and related procedures). Serial sections from the paraffin embedded material were used for immunohistochemical investigations. Immunohistochemical expression in glands and stroma was evaluated by the semi-quantitative H-score (ER-alpha, ER-beta, PR-A, PR-B, RCAS-1, Bcl-2, BAX, and Caspase-3).
  
  
  RESULTS
  The histomorphometric 4-class rule differentiates between presence and absence of cancers with a sensitivity of 80% and specificity of 77%. Several morphometric and immunohistochemical features were significantly different in cases with cancer and hyperplasia.
  
  
  CONCLUSIONS
  Histomorphometry seems superior in predicting coexistent carcinoma in high-risk endometrial hyperplasia and should be considered for clinical use.
authors.affiliation: Research Group of Gynecologic Oncology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Tromsø, Norway. anne.orbo@fagmed.uit.no
authors.forename: Anne
authors.initials: A
authors.lastname: Ørbo
authors.forename: Turid
authors.initials: T
authors.lastname: Kaino
authors.forename: Marit
authors.initials: M
authors.lastname: Arnes
authors.forename: Kurt
authors.initials: K
authors.lastname: Larsen
authors.forename: Inger
authors.initials: I
authors.lastname: Pettersen
authors.forename: Bjørn
authors.initials: B
authors.lastname: Moe
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D018269:Carcinoma, Endometrioid / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004714:Endometrial Hyperplasia / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone