Cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and Her-2/neu expression in ovarian cancer

Gynecol Oncol. 2002 May;85(2):305-10. doi: 10.1006/gyno.2002.6620.


Objectives: Cyclooxygenase-2 (COX-2) seems to be involved in critical steps of cancer onset and progression. Abnormalities of epidermal growth factor receptor (EGFR) and Her-2/neu have been actively investigated in ovarian cancer and associated with unfavorable clinical outcome. The involvement of COX-2 in ErbB family pathways has been proposed. We investigated by immunohistochemistry the expression of COX-2, EGFR, and Her-2/neu in a series of advanced primary ovarian cancers.

Methods: The study included 76 consecutive stage IIIC-IV ovarian cancer patients with measurable disease after first surgery. Immunohistochemistry was performed on paraffin-embedded sections with rabbit antiserum against COX-2, murine monoclonal antibody (MoAb) 300G9 against Her-2/neu, and monoclonal antibody 108 against EGFR.

Results: No association among COX-2, EGFR, and HER-2/neu was found. COX-2 positivity was found in a statistically significant higher percentage of unresponsive cases (80.0%) than in patients responding to chemotherapy (35.7%) (P = 0.0008). The association between COX-2 positivity and poor chance of response to treatment was retained in multivariate analysis. In the subgroup of patients who underwent explorative laparotomy COX-2-positive cases showed a shorter overall survival (P = 0.049).

Conclusions: COX-2 could represent a possible new marker of sensitivity to platin-based chemotherapy in ovarian cancer. The lack of association of COX-2 with EGFR or Her-2/neu suggests that the ability of COX-2 to predict tumor sensitivity to chemotherapy is not dependent on EGFR or Her-2/neu status and could be independently associated with prognosis. In this context, the availability of agents able to specifically interfere with COX-2, Her-2/neu, or EGFR tyrosine kinase is of potential interest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclooxygenase 2
  • ErbB Receptors / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / biosynthesis*
  • Membrane Proteins
  • Neoplasm Staging
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Receptor, ErbB-2 / biosynthesis*


  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • ErbB Receptors
  • Receptor, ErbB-2