title: Reduced retinoblastoma gene protein to Ki-67 ratio is an adverse prognostic indicator for ovarian adenocarcinoma patients.
abstract: OBJECTIVE
  Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia. However, the clinical significance of the deregulated expression of RB-1 in ovarian cancer remains undefined. We therefore conducted a retrospective investigation to clarify the relationships of RB-1 gene protein (pRb) to the percentage of cycling cells, clinicopathologic variables, other G1 interacting proteins and prognosis of nonbenign epithelial ovarian tumors.
  
  
  METHODS
  Paraffin-embedded tissue from 127 nonbenign epithelial ovarian tumors, including 44 of low malignant potential (LMP) and 83 primary ovarian adenocarcinomas, was stained immunohistochemically for pRb, p21(Cip1), p27(Kip1), p53, and Ki-67 antigen (a cell proliferation associated marker). Expression of these markers was correlated with clinicopathologic features and with overall survival of patients with adenocarcinomas.
  
  
  RESULTS
  pRb levels were significantly lower in LMP tumors than in carcinomas (P = 0.027). In the latter group, pRb expression decreased with increasing grade (I-II vs III) (P = 0.010), advancing stage (I-II vs III) (P < 0.001), and bulk residual disease (P = 0.014). pRb was not related to Ki-67 expression (P > 0.10) or to overall survival (P > 0.10) but a low pRb to Ki-67 ratio emerged as an important indicator of poor survival in univariate analysis in the entire cohort (P = 0.0076) and in the platinum-treated patients (P = 0.0162) as well as in multivariate analysis, along with histologic type and FIGO stage.
  
  
  CONCLUSIONS
  Diminished pRb levels are related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas. More importantly, pRb expression coupled with the percentage of Ki-67 positive cells is a better prognostic marker than pRb, Ki-67, or other G1 interacting proteins and supplements the information gained from traditional prognosticators.
authors.affiliation: Department of Pathology, National Capodistrian University of Athens, 115 27, Athens, Greece.
authors.forename: Anastasia E
authors.initials: AE
authors.lastname: Konstantinidou
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vassilopoulos
authors.forename: Artemis
authors.initials: A
authors.lastname: Tsenga
authors.forename: Irene
authors.initials: I
authors.lastname: Thymara
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Agapitos
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Davaris
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D012189:Retrospective Studies; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27