title: Exploratory study of ovarian intraepithelial neoplasia.
abstract: OBJECTIVE
  This was an exploratory study to test two hypotheses related to potential epithelial precursors to ovarian cancer: (a) histologically normal ovarian surface epithelium exhibited changes in the nuclear chromatin pattern, which indicate an ovarian abnormality, and (b) such changes were detectable in the ovarian surface epithelium of cancer-free subjects who were at high risk for ovarian cancer.
  
  
  METHODS
  Ovaries were carefully collected to avoid damage to the surface epithelium. Five-micron-thick histologic sections were cut and stained with H&E. High-resolution images were recorded from the ovarian surface epithelium and from the underlying stroma of ovaries from normal women (10 cases), women at high risk of developing ovarian cancer (7 cases), and histologically normal areas adjacent to ovarian cancer (3 cases). Karyometric features and measurements of nuclear abnormality were computed for 3,390 epithelial nuclei. Discriminant function analyses and unsupervised learning algorithms were employed to define deviations from normal and to identify the subpopulations of nuclei exhibiting these changes.
  
  
  RESULTS
  Epithelium from ovaries harboring a malignant lesion had changes in the nuclear chromatin pattern consistent with a second phenotype, which were not visually detected with histopathologic surveillance. This phenotype was also present in the ovaries obtained from women at increased risk of ovarian cancer, suggesting that it may represent a premalignant abnormality. These changes were statistically significant.
  
  
  CONCLUSIONS
  The observed changes in karyometric features were sufficiently distinct to warrant further study as both diagnostic and prognostic biomarkers for early detection and prevention of ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Arizona Cancer Center, Room 1968G, 1515 North Campbell Avenue, Tucson, AZ 85724-5024, USA. mbrewer@azcc.arizona.edu
authors.forename: Molly A
authors.initials: MA
authors.lastname: Brewer
authors.forename: James
authors.initials: J
authors.lastname: Ranger-Moore
authors.forename: Amy
authors.initials: A
authors.lastname: Baruche
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
authors.forename: Mark
authors.initials: M
authors.lastname: Greene
authors.forename: Deborah
authors.initials: D
authors.lastname: Thompson
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.forename: Peter H
authors.initials: PH
authors.lastname: Bartels
mesh_terms: D002278:Carcinoma in Situ / Q000473:pathology / Q000648:ultrastructure*; D002467:Cell Nucleus / Q000473:pathology / Q000648:ultrastructure; D002843:Chromatin / Q000648:ultrastructure; D004847:Epithelial Cells / Q000648:ultrastructure; D004848:Epithelium / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007620:Karyometry; D010051:Ovarian Neoplasms / Q000473:pathology / Q000648:ultrastructure*; D010053:Ovary / Q000166:cytology / Q000648:ultrastructure*; D011230:Precancerous Conditions / Q000473:pathology / Q000648:ultrastructure*; D012306:Risk
chemical_list: D002843:Chromatin