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. 2020 Feb;54(1):35-42.
doi: 10.1007/s13139-019-00632-8. Epub 2020 Jan 3.

Analysis Natrium Iodide Symporter Expression in Breast Cancer Subtypes for Radioiodine Therapy Response

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Free PMC article

Analysis Natrium Iodide Symporter Expression in Breast Cancer Subtypes for Radioiodine Therapy Response

Aisyah Elliyanti et al. Nucl Med Mol Imaging. 2020 Feb.
Free PMC article

Abstract

Purpose: This study investigates natrium iodide symporter (NIS) expression in three breast cancer subtypes to predict radioiodine response.

Materials and methods: Frozen breast tissues from triple negative (TN), human epidermal receptor 2 (HER2+), and luminal A cancers were used in this research. NIS protein expression in each subtype was analyzed using immunohistochemistry (IHC) and western blot (WB). Secondary data such as age, subtypes, and Ki 67 index were drawn from the surgical oncologist database. Breast cancer cell lines were used to investigate the effect of radioiodine by measuring cell proliferation.

Results: The forty-one breast cancer samples were analyzed consisted of the following subtypes: TN, HER2+, and luminal A were 58%, 22%, and 20% respectively. The stages of disease were 2A to 4A. Most of samples were at 3B. Ki 67 index of TN, HER2+, and luminal A were 21 ± 12, 19 ± 5, and 7 ± 3 respectively. The NIS expression was detected in 95% of samples in cytoplasm and/or cell membrane; 93% of samples were invasive breast carcinomas. Only 20% of the samples showed NIS expression at cell membrane; four samples were HER2+, and other four were TN subtypes. NIS membrane score was significantly positively correlated with Ki67 index, p = 0.04. NIS protein expression was detected at sizes 88 kDa, 50 kDa, and 27 kDa. Cell proliferation rate means of MDA-MB 231, SKBR3, and MCF7 cells were 81.6 ± 4, 10.6 ± 5, and 15.4 ± 13 respectively (p = 0.009).

Conclusion: NIS protein expression is detectable in breast cancer cells to varying degrees. HER2+ is the most likely to express NIS in the cell membrane followed by TN subtypes. This indicates that radioiodine could be used as a novel adjuvant treatment in breast cancer.

Keywords: Cell proliferation; Immunohistochemistry; Ki 67 index; Radioiodine therapy; Western blot.

Conflict of interest statement

Conflict of InterestAisyah Elliyanti, Dewi Rusnita, Nita Afriani, Yayi Dwina Billianti Susanto, Veronica Y Susilo, Sri Setiyowati, and Wirsma Arif Harahap declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Molecular markers expression in each breast cancer subtype. a The average of Ki 67 index based on the subtype. Asterisk (*) indicates significant difference p = 0.001. b The intensity of NIS expression in the cytoplasm in various breast cancer subtype
Fig. 2
Fig. 2
Immunohistochemistry of NIS expression in membrane from various breast cancer subtypes. a TN subtype. B HER2+ subtype. c Luminal A subtype. d Control positive (Graves’ disease). Arrows indicate the NIS expression in the membrane. The images are shown in × 400 magnification
Fig. 3
Fig. 3
Comparison of Ki 67 index between samples which positive NIS expressing membrane NIS (+); N = 8 and not expressing NIS (−); N = 33. Asterisk (*) indicates significant difference (p < 0.008)
Fig. 4
Fig. 4
NIS expression blotting in various breast cancer subtypes. a Western blot result. b NIS expression distribution in breast cancer subtypes
Fig. 5
Fig. 5
The proliferation rate of MDA-MB 231, SKBR3, and MCF7 cell lines. (p < 0.05). Asterisk (*) indicates significant difference (p < 0.05)

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