title: Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer.
abstract: Cyclooxygenase-2 (Cox-2) expression can induce mammary tumorigenesis in transgenic mice, and selective Cox-2 inhibitors are both chemopreventive and chemotherapeutic in rat models of breast cancer. We analyzed the expression of Cox-2 protein by immunohistochemistry in tissue array specimens of 1576 invasive breast cancers. Moderate to strong (elevated) expression of Cox-2 protein was observed in 37.4% of the tumors, and it was associated with unfavorable distant disease-free survival (P < 0.0001). Elevated Cox-2 expression was associated with a large tumor size, a high histological grade, a negative hormone receptor status, a high proliferation rate (identified by Ki-67), high p53 expression, and the presence of HER-2 oncogene amplification (P < 0.0001 for all comparisons), along with axillary node metastases and a ductal type of histology (P = 0.0001 and P = 0.0017, respectively). Interestingly, association with the unfavorable outcome was especially apparent in the subgroups defined by estrogen receptor positivity, low p53 expression, and no HER-2 amplification (P < 0.0001 for all comparisons). These results indicate that elevated Cox-2 expression is more common in breast cancers with poor prognostic characteristics and is associated with an unfavorable outcome. The present findings support efforts to initiate clinical trials on the efficacy of Cox-2 inhibitors in adjuvant treatment of breast cancer.
authors.affiliation: Department of Pathology, Molecular and Cancer Research Program, Helsinki University Central Hospital, P.O. Box 63 (Haartmaninkatu 8), FIN-00014 Helsinki, Finland. Ari.Ristimaki@hus.fi
authors.forename: Ari
authors.initials: A
authors.lastname: Ristimäki
authors.forename: Anna
authors.initials: A
authors.lastname: Sivula
authors.forename: Johan
authors.initials: J
authors.lastname: Lundin
authors.forename: Mikael
authors.initials: M
authors.lastname: Lundin
authors.forename: Tiina
authors.initials: T
authors.lastname: Salminen
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Jorma
authors.initials: J
authors.lastname: Isola
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000473:pathology; D018275:Carcinoma, Lobular / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases