title: Prognostic influence of cyclooxygenase-2 protein and mRNA expression in node-negative breast cancer patients.
abstract: BACKGROUND
  Cyclooxygenases (COX) play a key role in prostaglandin metabolism and are important for tumor development and progression. The aim of this study was to analyze the prognostic impact of COX-2 expression in a cohort of lymph node-negative breast cancer patients not treated in the adjuvant setting.
  
  
  METHODS
  COX-2 expression was determined by immunohistochemistry (IHC) in tumor tissue of 193 node-negative breast cancer patients. Additionally, mRNA expression was determined in corresponding tumor samples using microarray based gene-expression data. Univariate and multivariate Cox regression analyses adjusted for age at diagnosis, tumor size, histological grade, human epithelial growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) were performed to evaluate the association of both COX-2 protein and mRNA expression with survival. Survival rates were determined by the Kaplan-Meier method. Correlations between COX-2 expression and established prognostic factors were analyzed using the Chi-square test. A potential correlation between COX-2 protein expression and COX-2 mRNA expression was assessed utilizing the Kruscal-Wallis-H-test.
  
  
  RESULTS
  COX-2 protein expression was positive in 24.9% of the breast cancer samples. Univariate analysis showed that COX-2 protein expression was associated with shorter disease-free survival (DFS) (P = 0.0001), metastasis-free survival (MFS) (P = 0.002) as well as breast cancer specific overall survival (OS) (P = 0.043). In multivariate analysis COX-2 expression retained its significance independent of established prognostic factors for shorter DFS (P < 0.001, HR = 2.767, 95% CI = 1.563-4.901) and for inferior MFS (P = 0.002, HR = 2.7, 95% CI = 1.469-5.263) but not for OS (P = 0.096, HR = 1.929, 95% CI = 0.889-4.187). In contrast, COX-2 mRNA expression was not related to survival and failed to show a correlation with protein expression (P = 0.410).
  
  
  CONCLUSIONS
  The present findings support the hypothesis that COX-2 protein but not mRNA expression is associated with an unfavorable outcome in node-negative breast cancer.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sicking
authors.forename: Karlien
authors.initials: K
authors.lastname: Rommens
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Battista
authors.forename: Daniel
authors.initials: D
authors.lastname: Böhm
authors.forename: Susanne
authors.initials: S
authors.lastname: Gebhard
authors.forename: Antje
authors.initials: A
authors.lastname: Lebrecht
authors.forename: Cristina
authors.initials: C
authors.lastname: Cotarelo
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoffmann
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.affiliation: Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany. marcus.schmidt@unimedizin-mainz.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D051546:Cyclooxygenase 2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C496540:PTGS2 protein, human; C508053:ERBB2 protein, human