Heparanase and COX-2 expression as predictors of lymph node metastasis in large, high-grade breast tumors

Stephanie Gawthorpe, James E. Brown, Muhammad Arif, Peter Nightingale, Alan Nevill, Amtul R. Carmichael*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background/Aim: 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. Materials and 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). Conclusion: Expression of HPA appears to be a key mechanism by which large, highgrade breast tumors metastasize to regional lymph nodes, while COX-2 overexpression may be an independent predictor of lymph node positivity.

Original languageEnglish
Pages (from-to)2797-2800
Number of pages4
JournalAnticancer Research
Issue number6
Publication statusPublished - 30 Jun 2014

Bibliographical note

Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.


  • breast cancer
  • heparanase
  • lymph nodes
  • tumor grade


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