title: Expression and prognostic significance of cyclin D3 in ovarian adenocarcinomas.
abstract: Abnormal expression of cell cycle regulators may contribute to malignant transformation. However, the clinical significance of the expression of cyclin D3 in ovarian cancer remains undefined. We therefore conducted a retrospective investigation to address the role of this cell-cycle protein in this tumor. In our study, paraffin-embedded tissue from 109 nonbenign epithelial ovarian tumors, including 17 tumors of low malignant potential and 92 primary adenocarcinomas, was stained immunohistochemically for cyclin D3. Most of the cases had previously been stained for pRb, p21Cip1, p27Kip1, p53, and Ki-67 antigen. Expression of cyclin D3 was correlated with clinicopathologic features, the expression of other cell cycle regulators, and postoperative survival of patients. Cyclin D3 levels were significantly higher in tumors of low malignant potential than in adenocarcinomas (P = 0.0002). In the latter group, cyclin D3 expression decreased with increasing grade (P = 0.0004) and advancing stage (P = 0.0315). Cyclin D3 expression positively correlated with pRb, p21Cip1, and p27Kip1 levels (P = 0.0021; P = 0.0036; P < 0.0001, respectively) and negatively with p53 and Ki-67 (P = 0.0003; P < 0.0001). Absent cyclin D3 expression was an important indicator of poor survival in univariate analysis in the entire cohort (P > 0.00010) and in the platinum-treated patients (P = 0.001) and in multivariate analysis (P = 0.044). Our results demonstrate that absent or decreased cyclin D3 expression is adversely related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas and is combined with a better prognosis, suggesting that cyclin D3 may have a biological role distinct from that of other G1 cyclins which is possibly regulated through interaction with other cell cycle genes.
authors: Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. glevidou@med.uoa.gr
authors: Georgia
authors: G
authors: Levidou
authors: Penelope
authors: P
authors: Korkolopoulou
authors: Irene
authors: I
authors: Thymara
authors: Ioannis
authors: I
authors: Vassilopoulos
authors: Angelica A
authors: AA
authors: Saetta
authors: Hariclia
authors: H
authors: Gakiopoulou
authors: Anastasia
authors: A
authors: Konstantinidou
authors: Evi
authors: E
authors: Kairi-Vassilatou
authors: Kitty
authors: K
authors: Pavlakis
authors: Efstratios
authors: E
authors: Patsouris
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D056743:Cyclin D3; D016213:Cyclins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins