High cyclooxygenase-2 Expression in Stage IB Cervical Cancer With Lymph Node Metastasis or Parametrial Invasion

Gynecol Oncol. 2000 Mar;76(3):320-5. doi: 10.1006/gyno.1999.5690.


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 proinflammatory cytokines, and suggestions have been made that overexpression of COX-2 suppresses apoptosis and is directly related to tumor growth. We have attempted to determine a relationship between 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 IB uterine cervical cancer patients who underwent surgery at Ajou University Hospital. There were 12 cases with lymph node or parametrial involvement. All tissues were subjected 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 were separated into tumor surface, tumor stroma, and invasion site portions, in which decreased apoptosis was observed in the invasion sites. COX-2 expression was observed in all tumor tissues and was especially strong in the tumor invasion site. Therefore, it is suggested that COX-2 expression may suppress cell apoptosis at the tumor invasion site. When COX-2 expression was investigated according to the groups with regard to the presence of lymph node or parametrial involvement, there was a statistically significant (Mann-Whitney U test) COX-2 expression difference in the tumor invasion site (P value = 0.040) and the tumor 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 cervical cancer may downregulate apoptotic processes and thus enhance tumor invasion and metastasis.

MeSH terms

  • Apoptosis
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Lymphatic Metastasis
  • Membrane Proteins
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / pathology*


  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases