Ki-67 as an independent prognostic factor in an unselected cohort of patients with ovarian cancer: results of an explorative, retrospective study

Oncol Rep. 2014 May;31(5):2213-9. doi: 10.3892/or.2014.3079. Epub 2014 Mar 11.

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.

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Carcinoma, Ovarian Epithelial
  • Cell Proliferation
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Humans
  • Ki-67 Antigen / biosynthesis*
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / mortality*
  • Neoplasms, Glandular and Epithelial / therapy*
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / therapy*
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Retrospective Studies
  • Tumor Burden
  • Urokinase-Type Plasminogen Activator / biosynthesis

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Plasminogen Activator Inhibitor 1
  • Receptors, Estrogen
  • Receptors, Progesterone
  • SERPINE1 protein, human
  • Urokinase-Type Plasminogen Activator