title: Cyclooxygenase-2 expression in primary breast cancers predicts dissemination of cancer cells to the bone marrow.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX2) plays a role in breast cancer progression at various stages starting from pre-malignant phenotype to clinical metastasis. Breast cancer metastasizes commonly to the bone and preclinical studies suggest an involvement of COX2 in this process. Detection of disseminated tumor cells in the bone marrow of patients at the time of surgery correlates with the subsequent development of clinical bone metastasis. Therefore, to investigate whether COX2 is important for breast cancer metastasis in humans, we analyzed COX2 protein expression by immunostaining of primary tumors from 112 operable stages I, II, or III patients and determined its correlation with bone marrow micrometastasis (BMM).
  
  
  METHODS
  We detected COX2 protein in primary tumors by immunostaining with a monoclonal antibody, and tumor cells present in the bone marrow by immunostaining for epithelial cytokeratins and by morphological criteria.
  
  
  RESULTS
  COX2 expression in primary breast cancer correlated with BMM in a highly statistically significant manner (P = 0.006). Our statistical analyses of correlations of the COX2 positivity in primary tumor with other clinically relevant indicators revealed that COX2 positivity correlates with high nuclear grade (P = 0.0004). Furthermore, we were able to detect COX2 protein in BMM by immunostaining.
  
  
  CONCLUSIONS
  These studies indicate that COX2 produced in primary breast cancer cells may be vital to the initial development of BMM that may subsequently lead to osteolytic bone metastases in patients with breast cancer, and that COX2 inhibitors may be useful in halting this process.
authors.affiliation: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA. alucci@mdanderson.org
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: Balraj
authors.initials: B
authors.lastname: Singh
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bedrosian
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: James
authors.initials: J
authors.lastname: Reuben
authors.forename: Kristine
authors.initials: K
authors.lastname: Broglio
authors.forename: Kailash
authors.initials: K
authors.lastname: Mosalpuria
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Lodhi
authors.forename: Laura
authors.initials: L
authors.lastname: Vincent
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D019046:Bone Marrow Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2