Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma.
BACKGROUND
Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. The authors investigated the prognostic impact of expression of the cyclooxygenase (COX) isoforms, COX-1 and COX-2, on disease-free survival and progression-free survival in patients with primary breast carcinoma as well as the association between COX expression and other clinicopathologic parameters.


METHODS
In this study COX isoform expression was determined by immunohistochemistry in a cohort of 221 patients with primary breast carcinoma.


RESULTS
Expression of COX-2 was detected in 36% of breast carcinoma samples and was associated significantly with several clinicopathologic parameters, including positive lymph node status (P < 0.0005), larger tumor size (P < 0.0005), poor differentiation (P < 0.0005), vascular invasion (P = 0.03), and negative estrogen receptor status (P = 0.04). In contrast, COX-1 was expressed in 45% of tumors and was associated with smaller tumor size (P = 0.02) and with negative lymph node status (P = 0.01). In a univariate survival analysis, a significant association was observed between elevated COX-2 expression and decreases in disease-free survival (P = 0.0007) and overall survival (P = 0.02). In a multivariate analysis, expression of COX-2 was of borderline significance for disease-free survival (relative risk, 1.90; 95% confidence interval, 1.00-3.59), adjusting for tumor size, histologic grade, number of positive lymph nodes, and patient age. Elevated expression of COX-1 in tumor tissue had no statistically significant influence on patient prognosis.


CONCLUSIONS
The current data suggest that increased expression of COX-2 may play a role in the progression of primary breast carcinoma. It remains to be investigated whether treatment with selective inhibitors of COX-2 may be an additional therapeutic option for patients with breast carcinoma.
Denkert
Carsten
C
Institute of Pathology, Charité Hospital, Berlin, Germany. carsten.denkert@charite.de
Winzer
Klaus-Jürgen
KJ
Müller
Berit-Maria
BM
Weichert
Wilko
W
Pest
Sören
S
Köbel
Martin
M
Kristiansen
Glen
G
Reles
Angela
A
Siegert
Antje
A
Guski
Hans
H
Hauptmann
Steffen
S
D000328:Adult; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008565:Membrane Proteins; D008875:Middle Aged; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D016019:Survival Analysis
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases