title: Expression of cyclin D1 in normal, metaplastic, hyperplastic endometrium and endometrioid carcinoma suggests a role in endometrial carcinogenesis.
abstract: BACKGROUND
  Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium.
  
  
  METHODS
  Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features.
  
  
  RESULTS
  Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia.
  
  
  CONCLUSIONS
  Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium.
authors.affiliation: Department of Pathology, Women and Infants Hospital, Brown University Medical School, Providence, RI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ruhul Quddus
authors.forename: Predrag
authors.initials: P
authors.lastname: Latkovich
authors.forename: William J
authors.initials: WJ
authors.lastname: Castellani
authors.forename: C
authors.initials: C
authors.lastname: James Sung
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Steinhoff
authors.forename: Robert C
authors.initials: RC
authors.lastname: Briggs
authors.forename: Roberto N
authors.initials: RN
authors.lastname: Miranda
mesh_terms: D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007124:Immunoenzyme Techniques; D008679:Metaplasia / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology
chemical_list: D019938:Cyclin D1