title: Heparanase and COX-2 expression as predictors of lymph node metastasis in large, high-grade breast tumors.
abstract: OBJECTIVE
  Heparanase (HPA) contributes to breast cancer metastasis by facilitating the breakdown of the basement membrane and extracellular matrix. High expression of HPA is thought to be associated with increased nodal involvement and poor survival in patients with breast cancer. Overexpression of cyclooxygenase-2 (COX-2) in breast cancer is associated with indicators of poor prognosis such as lymph node metastasis, poor differentiation, and large tumor size. The underlying mechanism by which HPA and COX-2 overexpression increases the metastatic potential of breast cancer is not fully-understood. To enhance our understanding over these mechanisms, we aimed to investigate the relationship between the size of the tumor and HPA expression, tumor grade as well as lymph node status in patients with breast cancer.
  
  
  METHODS
  Immunohistochemical analysis of HPA and COX-2 expression was performed on 246 breast tumor samples. The expression of HPA was correlated with COX-2 expression, tumor grade, lymph node status, oestrogen receptor status.
  
  
  RESULTS
  The overexpression of HPA and COX-2 was associated with increased likelihood of lymph node positivity in large, high-grade tumors. High-grade tumors with size greater than 20 mm, that overexpressed HPA, were 4-times more likely to be associated with lymph node involvement (OR 4.71, CI 1.21-18.25). Whereas, tumors greater than 20 mm in size were 5-times more likely to metastasize to the regional lymph nodes, if associated with overexpression of COX-2 (OR 5.5, CI 1.2-24.8).
  
  
  CONCLUSIONS
  Expression of HPA appears to be a key mechanism by which large, high-grade breast tumors metastasize to regional lymph nodes, while COX-2 overexpression may be an independent predictor of lymph node positivity.
authors.affiliation: Department of Histopathology, Russell's Hall Hospital, Dudley, United Kingdom.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gawthorpe
authors.affiliation: Aston Research Centre for Healthy Ageing and School of Life and Health Sciences, Aston University, Birmingham, United Kingdom.
authors.forename: James E
authors.initials: JE
authors.lastname: Brown
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham, United Kingdom.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Arif
authors.affiliation: Wolfson Computer Laboratory, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Nightingale
authors.affiliation: School of Sport, Performing Arts and Leisure, University of Wolverhampton, Walsall, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Nevill
authors.affiliation: Department of Surgery, Russell's Hall Hospital, Dudley, United Kingdom Amtul.Carmichael@dgh.nhs.uk.
authors.forename: Amtul R
authors.initials: AR
authors.lastname: Carmichael
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000556:secondary; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D000099175:Heparanase
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D005966:Glucuronidase; D000099175:Heparanase; C496540:PTGS2 protein, human
keywords: Breast cancer; heparanase; lymph nodes; tumor grade