Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors

J Ovarian Res. 2018 Feb 27;11(1):17. doi: 10.1186/s13048-018-0389-9.

Abstract

Background: High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 expression and its relation to survival is less clear. Here, we evaluated COX expression and associations with survival outcomes between type I (clear cell, mucinous, low grade endometrioid and low grade serous) and type II (high grade serous and high grade endometrioid) ovarian tumors.

Methods: We developed and validated a new COX-1 antibody, and conducted immunohistochemical (IHC) staining for COX-1 and COX-2 on a tissue microarray (TMA) of 190 primary ovarian tumors. In addition to standard IHC scoring and H-scores to combine the percentage of positive cells and staining intensity, we also measured COX-1 and COX-2 mRNA expression by QPCR. High expression was defined as greater than or equal to median values. Clinical characteristics and disease outcomes were ascertained from medical records. Associations with disease-free survival (DFS) and overall survival (OS) were quantified by hazard ratios (HRs) and confidence intervals (CIs) from proportional hazards regression.

Results: Type I tumors had high COX-2 expression, while type II tumors had high COX-1 expression. In multivariable adjusted regression models, higher COX-1 mRNA expression was associated with shorter DFS (HR: 6.37, 95% CI: 1.84-22.01) and OS (HR: 2.26, 95% CI: 1.04-4.91), while higher H-scores for COX-2 expression were associated with shorter DFS (HR: 1.92, 95% CI: 1.06-3.49). Stratified analysis indicated that COX-2 was significantly associated with DFS among cases with Type II tumors (HR: 1.93, 95% CI: 1.06-3.53).

Conclusions: These findings suggest that ovarian tumor type contributes to differences in COX expression levels and associations with survival.

Keywords: Cyclooxygenase; Ovarian cancer; Survival analysis; Tumor subtype.

MeSH terms

  • Aged
  • Biomarkers, Tumor*
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Proportional Hazards Models
  • Prostaglandin-Endoperoxide Synthases / genetics*

Substances

  • Biomarkers, Tumor
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases