High Cyclooxygenase-2 Expression in Stage IB Cervical Cancer with Lymph Node Metastasis or Parametrial Invasion

Abstract

Objective: the enzymes cyclooxygenase(COX)-1 and -2 are necessary for the synthesis of prostaglandins. COX-2 is usually absent in normal cells and is upregulated and expressed as a product of the "immediate early" gene during inflammatory processes. In previous studies, the expression of COX-2 has been shown to be induced by prointlammatory cytockines, and suggestions have been made that overexpression of COX-2 supresses apoptosis and is directly related to tumor growth. We the authors have attempted to determine a relationship between the tumor invasion and metastasis of uterine cervical cancer and COX and apoptosis by comparing the protein expression of apoptosis and COX-I and COX-2 in tumor tissues confirmed with cytokeratin, and therefe determine the clinicopathologic risk factors. Materials and methods: The subjects were 18 patients who were FIGO stage IB uterine cervical cancer patients who underwent surgery at the Ajou University Medical Center. The 18 cases were comprised of 12 cases of squamous cell carcinoma, 3 cases each of adenocarcinoma and adenosquamous carcinoma. There were 9 cases with lymph node or prarametrial involvement and 13 cases with lymphvascular space involvement. All tissues obtained from the cases were subject to immunohistochemical staining for COX-1, -2 and TUNEL method for apoptosis detection, and the following results were obtained. Results: Tumor tissues confirmed by cytokeratin wae separated into tumor surface, tumor stroma, and invasion site portions, and in which increased apoptosis was observed in the tumor surface and tumor stmma, but not in the invasion sites. COX-2 expression was observed in all tumor tissues, which was especially strong in the tumor invasion site. Therefore, it is suggested that COX-2 expression may supress cell apoptosis at the site of tumor invasion. When COX-2 expression was investigated when the cases were divided into groups with regard to the presence or absence of lymph node or parametrial involvement, there was statistically significant (Mann-Whitney U test) COX-2 expression seen microscopically in the tumor stroma (p-value" 0.028) and tumor invasion site (p-value" 0.040) compared to the tumor surface (p-value" 0.499). In other words, in surgically treated stage IB cervical cancer patients, COX-2 was significantly expressed when lymph node or parametrial involvement was present. Conclusions: These results suggest that the expression of COX-2 in stage IB cervical cancer patients may downregulate apoptosic processes and thus enhances tumor invasion and metastasis.