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Prognostic significance of the expression of GFR?1, GFR?3 and syndecan-3, proteins binding ARTEMIN, in mammary carcinoma.

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 GFR?1, GFR?3 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 GFR?1 and GFR?3, 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 GFR?1 and GFR?3 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 GFR?1 or GFR?3, 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 GFR?1 and GFR?3 expression with survival outcome observed herein were restricted to ER negative or HER-2 negative mammary carcinoma.

Conclusions

The expression of GFR?1 and/or GFR?3, especially when combined with ARTN expression, may be useful predictors of disease progression and outcome in specific subtypes of mammary carcinoma.

SUBMITTER: Wu ZS

PROVIDER: S-EPMC3562211 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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

Wu Zheng-Sheng ZS Pandey Vijay V Wu Wen-Yong WY Ye Shan S Zhu Tao T Lobie Peter E PE

BMC cancer 20130126

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 23351331

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