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

Beeghly-Fadiel A, Wilson AJ, Keene S, El Ramahi M, Xu S, Marnett LJ, Fadare O, Crispens MA, Khabele D
J Ovarian Res. 2018 11 (1): 17

PMID: 29482584 · PMCID: PMC5828488 · DOI:10.1186/s13048-018-0389-9

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.

MeSH Terms (16)

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

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