Expression of cyclooxygenase-2 and its relationship to p53 accumulation in ovarian adenocarcinomas

Abstract

To investigate cyclooxygenase-2 (COX-2) expression and its relationship to p53 accumulation in ovarian adenocarcinomas, COX-2 and p53 protein expressions were examined by immunohistochemistry in 86 ovarian adenocarcinomas and six normal ovaries. In addition, COX-2 mRNA expression level was examined by semi-quantitative PCR in 36 ovarian adenocarcinomas. Neither COX-2 expression nor p53 accumulation were detected in normal ovarian surface epithelium or germinal inclusion cyst epithelial cells. In contrast, COX-2 protein expression was detected in 31.4% of adenocarcinomas, and p53 protein accumulation was found in 30.2% of adenocarcinomas. A significantly higher COX-2 expression rate was observed in endometrioid adenocarcinomas than in either mucinous (p=0.019) or clear cell (p=0.021) adenocarcinomas, and a significantly higher p53 accumulation rate was observed in serous adenocarcinomas compared to clear cell adenocarcinomas (p=0.015). p53 accumulation correlated with advanced clinical stage (stage I vs. stage II/III/IV: p=0.007), whereas no correlation was found between COX-2 expression and clinical stage. There was a significant positive correlation between COX-2 expression and p53 accumulation status (p=0.003). Log-rank testing showed that p53 accumulation was significantly correlated with poor patient survival (p=0.004), whereas no correlation was found between COX-2 expression and survival. COX-2 mRNA expression was detected in 72.2% of ovarian adenocarcinomas, and a significant correlation between COX-2 mRNA expression status and immunoreactivity (p=0.023) was observed. These results suggest that COX-2 expression might play an important role in ovarian cancer development and that COX-2 expression in ovarian adenocarcinomas is frequently associated with p53 protein accumulation. COX-2 overexpression in ovarian cancer cells might partly be caused by dysfunctional p53.