Expression of Sodium Iodide Symporter in Breast Cancer Tissue after Thyroid Cancer
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Background and Objectives: Radioactive iodine (RAI) therapy may be associated with the risk of breast cancer (BC) among thyroid cancer (TC) patients, and sodium iodide symporter (NIS) is thought to mediate this association. This study examined NIS expression and hormone receptors in BC that occurred after TC (TC→BC cases). Materials and Methods: Tissue microarrays with paired BC and normal breast tissues were constructed from 39 of TC→BC cases with a latency period ≥2 years and 36 age-matched BC patients. The expression of NIS, estrogen receptor (ERα and ERβ), and thyroid hormone receptor (TRα and TRβ) was evaluated by immunohistochemistry. Results: The frequency of NIS expression was higher in TC→BC cases compared with BC controls across both cancer tissues (61.8% vs. 21.9%, p=0.001) and normal (55.3% vs. 27.6%, p=0.028) tissues. In TC→BC cases, NIS expression was associated with prior RAI therapy while the overall free thyroxine levels measured during the latent period showed no association. ERα and TRα expression was more frequently observed in TC→BC cases, and their expression was associated with NIS expression independently of RAI therapy in cancer tissues. Conclusion: NIS expression was upregulated in BC tissues with known TC, which might be influenced by both prior RAI therapy and the hormone receptor status in BC tissues. Further studies are needed to clarify the molecular mechanism of their association.
Abstract
Background and Objectives: Radioactive iodine (RAI) therapy may be associated with the risk of breast cancer (BC) among thyroid cancer (TC) patients, and sodium iodide symporter (NIS) is thought to mediate this association. This study examined NIS expression and hormone receptors in BC that occurred after TC (TC→BC cases). Materials and Methods: Tissue microarrays with paired BC and normal breast tissues were constructed from 39 of TC→BC cases with a latency period ≥2 years and 36 age-matched BC patients. The expression of NIS, estrogen receptor (ERα and ERβ), and thyroid hormone receptor (TRα and TRβ) was evaluated by immunohistochemistry. Results: The frequency of NIS expression was higher in TC→BC cases compared with BC controls across both cancer tissues (61.8% vs. 21.9%, p=0.001) and normal (55.3% vs. 27.6%, p=0.028) tissues. In TC→BC cases, NIS expression was associated with prior RAI therapy while the overall free thyroxine levels measured during the latent period showed no association. ERα and TRα expression was more frequently observed in TC→BC cases, and their expression was associated with NIS expression independently of RAI therapy in cancer tissues. Conclusion: NIS expression was upregulated in BC tissues with known TC, which might be influenced by both prior RAI therapy and the hormone receptor status in BC tissues. Further studies are needed to clarify the molecular mechanism of their association.