title: Ki-67 as an independent prognostic factor in an unselected cohort of patients with ovarian cancer: results of an explorative, retrospective study.
abstract: The identification of prognostic markers has clinical implications in epithelial ovarian carcinoma (EOC). Here, we studied markers for proliferation (Ki-67), endocrine regulation [progesterone receptor (PR), estrogen receptor (ER)], and invasion [urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1)]. All patients with available follow-up information and EOC tissue, who were treated at our institution between 1997 and 2004, were enrolled in the present study. Expression of Ki-67, PR and ER was determined by immunohistochemical analyses. uPA and PAI-1 antigen levels were determined using enzyme‑linked immunosorbent assays. One hundred and eight patients entered the present study. The median follow-up time was 43.3 (range 11.4-68.0) months. In multivariable Cox regression analyses, Ki-67 expression showed an independent negative impact on disease-free survival (DFS) and overall survival (OS) [hazard ratio (HR) for DFS, 11.5; 95% confidence interval (CI), 2.64-49.7; p=0.001 and HR for OS, 21.2; 95% CI, 9.9-113.1; p<0.001]. After cut-off optimization, PR expression showed an independent positive impact on prognosis (HR for DFS, 0.15; 95% CI, 0.03-0.68; p=0.014 and HR for OS, 0.13; 95% CI, 0.03‑0.68; p=0.016). Furthermore, postoperative residual tumor burden and completeness of chemotherapy determined the prognosis. ER, uPA and PAI-1 were not associated with survival. PR and ER, and postoperative residual tumor burden and tumor stage showed a strong correlation in an explorative Spearman's rank correlation coefficient (rho=0.759 and rho=0.426, respectively). Ki-67 and cut-off optimized PR are independently associated with the prognosis of EOC. Further prospective studies are warranted to confirm these associations and to elucidate the underlying mechanisms.
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Centre Mainz, D-55131 Mainz, Germany.
authors.forename: Marco Johannes
authors.initials: MJ
authors.lastname: Battista
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Centre Mainz, D-55131 Mainz, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Mantai
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Centre Mainz, D-55131 Mainz, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sicking
authors.affiliation: Department of Pathology, University Medical Centre Mainz, D-55131 Mainz, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cotarelo
authors.affiliation: Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre Mainz, D-55131 Mainz, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Weyer
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Centre Mainz, D-55131 Mainz, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Lebrecht
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Centre Mainz, D-55131 Mainz, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Centre Mainz, D-55131 Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000401:mortality* / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000401:mortality* / Q000628:therapy*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D012189:Retrospective Studies; D047368:Tumor Burden; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D017395:Plasminogen Activator Inhibitor 1; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C051321:SERPINE1 protein, human; D014568:Urokinase-Type Plasminogen Activator