Cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and Her-2/neu expression in ovarian cancer.
OBJECTIVE
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.
Ferrandina
G
G
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy.
Ranelletti
F O
FO
Lauriola
L
L
Fanfani
F
F
Legge
F
F
Mottolese
M
M
Nicotra
M R
MR
Natali
P G
PG
Zakut
V H
VH
Scambia
G
G
D051546:Cyclooxygenase 2; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*
D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; C496540:PTGS2 protein, human