title: Nuclear P27 expression in benign, borderline (LMP) and invasive tumors of the ovary and its association with prognosis: a gynecologic oncology group study.
abstract: OBJECTIVE
  Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials.
  
  
  METHODS
  An immunohistochemistry assay was used to detect p27 in formalin-fixed paraffin-embedded ovarian tumors from 3 distinct sources.
  
  
  RESULTS
  Among the initial 91 ovarian tumors tested, low p27 expression (<50% positive cells) was observed in 5.4% of non-invasive tumors versus 42.6% of invasive tumors (p<0.001). In 145 ovarian cancers with high-risk early stage disease, 16.5% exhibited low p27 expression, and categorized p27 was not associated with age, race, or performance status. Low expression of p27 was common in poorly differentiated tumors (35.7%) compared to moderately (15.0%) and well (9.5%) differentiated tumors (p=0.024) and rare in clear cell carcinomas (2.4%) compared to other histologies (p=0.014). In the 139 cancers with advanced disease, 60% displayed low p27 expression, and categorized p27 expression was not associated with age, race, performance status, tumor grade, histologic subtype, measurable disease status or survival. Exploratory analyses revealed an association of cyclin E to p27 ratio >1.0 with an increased risk of death (hazard ratio=1.53; p=0.017).
  
  
  CONCLUSIONS
  Low p27 expression could be associated with malignant transformation of the ovarian epithelium and FIGO stage. A cyclin E to p27 ratio >1.0 may be associated with shorter survival in these patients. Further study is required to confirm the trend for increased recurrences with low p27 expression in early stage disease.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Walter Reed Army Medical Center, Washington, DC 20307, USA.
authors.forename: John
authors.initials: J
authors.lastname: Farley
authors.forename: Leia M
authors.initials: LM
authors.lastname: Smith
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: Mark F
authors.initials: MF
authors.lastname: Brady
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bell
authors.forename: William
authors.initials: W
authors.lastname: McGuire
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
mesh_terms: D000368:Aged; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D003430:Cross-Sectional Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis
chemical_list: C436291:CDKN1B protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27