Shigemasa Kazushi, Tian Xiurong, Gu Lijun, Shiroyama Yuko, Nagai Nobutaka, Ohama Koso
Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan.
Int J Oncol. 2003 Jan;22(1):99-105.
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.
为研究环氧化酶-2（COX-2）在卵巢腺癌中的表达及其与p53蓄积的关系，采用免疫组织化学方法检测了86例卵巢腺癌及6例正常卵巢组织中COX-2和p53蛋白的表达。此外，采用半定量PCR检测了36例卵巢腺癌组织中COX-2 mRNA的表达水平。在正常卵巢表面上皮或生发包涵囊肿上皮细胞中均未检测到COX-2表达及p53蓄积。相反，31.4%的腺癌组织中检测到COX-2蛋白表达，30.2%的腺癌组织中发现p53蛋白蓄积。子宫内膜样腺癌中COX-2表达率显著高于黏液性（p=0.019）或透明细胞（p=0.021）腺癌，浆液性腺癌中p53蓄积率显著高于透明细胞腺癌（p=0.015）。p53蓄积与临床分期进展相关（Ⅰ期与Ⅱ/Ⅲ/Ⅳ期：p=0.007），而COX-2表达与临床分期无相关性。COX-2表达与p53蓄积状态之间存在显著正相关（p=0.003）。对数秩检验显示，p53蓄积与患者生存率低显著相关（p=0.004），而COX-2表达与生存率无相关性。72.2%的卵巢腺癌组织中检测到COX-2 mRNA表达，且COX-2 mRNA表达状态与免疫反应性之间存在显著相关性（p=0.023）。这些结果提示，COX-2表达可能在卵巢癌发生发展中起重要作用，且卵巢腺癌中COX-2表达常与p53蛋白蓄积相关。卵巢癌细胞中COX-2过表达可能部分由p53功能异常所致。
