High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion

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 durin g inflammatory processes. In previous studies, the expression of COX-2 has been shown to be induced by proinflammatory cytokines, and suggestions have been made that overexpression of COX-2 suppresses apoptosis and is directl y related to tumor growth. We have attempted to determine a relationship be tween tumor invasion and metastasis of uterine cervical cancer and COX and apoptosis by comparing the protein expression of apoptosis, COX-1, and COX- 2 in tumor tissues. Methods. The subjects were 36 patients who were FIGO stage TS uterine cervi cal cancer patients who underwent surgery at Ajou University Hospital. Ther e were 12 cases with lymph node or parametrial involvement. All tissues wer e subjected to immunohistochemical staining for COX-I, -2, and TUNEL method for apoptosis detection, and the following results were obtained. Results. Tumor tissues confirmed by cytokeratin were separated into tumor s urface, tumor stroma, and invasion site portions, in which decreased apopto sis was observed in the invasion sites. COX-2 expression was observed in al l tumor tissues and was especially strong in the tumor invasion site. There fore, it is suggested that COX-2 expression may suppress cell apoptosis at the tumor invasion site. When COX-2 expression was investigated according t o the groups with regard to the presence of lymph node or parametrial invol vement, there was a statistically significant (Mann-Whitney U test) COX-2 e xpression difference in the tumor invasion site (P value = 0.040) and the t umor stroma (P value = 0.028). Conclusions. In surgically treated stage IB cervical cancer patients, COX-2 was significantly expressed when lymph node or parametrial involvement was present. These results suggest that the expression of COX-2 in stage IB ce rvical cancer may downregulate apoptosic processes and thus enhance tumor i nvasion and metastasis. a (C)2000 Academic Press.