Prognostic significance of the expression of GFRα1, GFRα3 and syndecan-3, proteins binding ARTEMIN, in mammary carcinoma.
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.
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.
Zheng-Sheng
ZS
Wu
Vijay
V
Pandey
Wen-Yong
WY
Wu
Shan
S
Ye
Tao
T
Zhu
Peter E
PE
Lobie
D002288:Adenocarcinoma, Mucinous / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry; D018275:Carcinoma, Lobular / Q000737:chemistry; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000032:analysis*; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012307:Risk Factors; D053670:Syndecan-3 / Q000032:analysis* / Q000235:genetics; D013997:Time Factors
D014408:Biomarkers, Tumor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D053670:Syndecan-3; C490886:ARTN protein, human; C494987:GFRA1 protein, human; C494993:GFRA3 protein, human; C508301:SDC3 protein, human; C508053:ERBB2 protein, human