alexa Abstract | Differential Expression of the Na+/I- Symporter by Endocrine Receptor Status: A Potential New Therapeutic Target in Estrogen Receptor Negative High Grade Breast Cancers

Translational Biomedicine
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Research Article Open Access

Abstract

Purpose: Expression of the sodium-iodide (Na+/I-) symporter (NIS) in thyroid cancer accounts for the success of radioactive iodine (131I) ablation of remnants or metastases following thyroidectomy. Breast cancer (BC) is one of the other malignancies that express functional NIS. The aim of the present study was to evaluate the expression and localisation of NIS according to BC subtype.

Materials and methods: Ninety predominantly high grade primary BC were independently evaluated for NIS expression and cellular localization (membranous and/or cytoplasmic) by immuno-histochemistry. mRNA expression of the NIS (SLC5A5) gene was analyzed across 18 publicly available whole genome microarray datasets including 3,091 primary breast tumors. NIS expression was compared with clinical and pathological tumor characteristics.

Results: Cytoplasmic (cNIS) and membrane (mNIS) immunoreactivity was more frequently observed in estrogen receptor (ER) and progesterone receptor (PR) negative (ER-/PR-) tumors (45% mNIS and 67% cNIS) than in ER and PR positive (ER+PR+) tumors (7% mNIS and 20% cNIS) (p<0.001). cNIS staining was not present in only 4% (1/25) of the tumors with mNIS staining.

NIS mRNA expression was higher in ER negative tumors defined by local pathological ER evaluation (p=0.013) or microarray classification (p=0.011).

HER2 status had no influence on NIS expression regardless of the analytical method considered.

Conclusions: NIS expression is increased in ER negative breast cancer. ER negative breast cancer should be targeted for clinical studies evaluating radioactive iodine therapy including strategies to mobilize cytoplasmic NIS to the cell membrane and enhance the activity of 131I in these cancers.

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Author(s): Bourgeois P Bedard PL Sirtaine N Ameye L Veys I Noterman D Hertens D Loi S Singhal SK Paesmans M Franc B Nogaret JM Sotiriou C Awada A Larsimont D

Keywords

Breast cancer, Natrium-iodide symporter, Endocrine receptor, Molecular Therapy,Cancer Drug Targets,Breast Cancer

 
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