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Open Access Research article

Prognostic significance of the expression of GFRα1, GFRα3 and Syndecan-3, proteins binding ARTEMIN, in mammary carcinoma

Zheng-Sheng Wu12, Vijay Pandey3, Wen-Yong Wu4, Shan Ye2, Tao Zhu1* and Peter E Lobie35*

Author affiliations

1 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China

2 Department of Pathology, Anhui Medical University, Hefei, Anhui, People's Republic of China

3 Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Centre for Life Sciences, #03-06C, 28 Medical Drive, Singapore, 117456, Singapore

4 Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Anhui, Hefei, Anhui, People's Republic of China

5 National Cancer Science Institute of Singapore, National University Health system, Singapore, Singapore

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Citation and License

BMC Cancer 2013, 13:34  doi:10.1186/1471-2407-13-34

Published: 26 January 2013

Abstract

Background

Artemin (ARTN) has been implicated in promoting oncogenicity, tumor growth and invasiveness in diverse human malignancies. However, the clinical and prognostic significance of upstream ligand binding components, potentially mediating ARTN oncogenicity, largely remain to be determined.

Methods

We determined the mRNA and protein expression of three proteins demonstrated to bind ARTN, namely GFRα1, GFRα3 and Syndecan-3 (SDC3), in benign breast disease and mammary carcinoma by in situ hybridization and immunohistochemistry, respectively. Their prognostic significance combined with ARTN expression was also investigated in mammary carcinoma.

Results

The expression of GFRα1 and GFRα3, but not SDC3, was significantly increased in mammary carcinoma and positively associated with tumor lymph node metastases, higher clinical stage and HER-2 positivity. Moreover, both GFRα1 and GFRα3 expression were significantly associated with survival outcome of patients with mammary carcinoma by univariate and multivariate analyses, whereas expression of SDC3 was not. Co-expression of ARTN with either GFRα1 or GFRα3, but not SDC3, produced synergistic increases in the odds ratio for both relapse-free and overall survival in patients with mammary carcinoma. Furthermore, significant association of GFRα1 and GFRα3 expression with survival outcome observed herein were restricted to ER negative or HER-2 negative mammary carcinoma.

Conclusions

The expression of GFRα1 and/or GFRα3, especially when combined with ARTN expression, may be useful predictors of disease progression and outcome in specific subtypes of mammary carcinoma.

Keywords:
ARTN; GFRα1; GFRα3; SDC3; Mammary carcinoma; Survival