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

Aisyah Elliyanti; Dewi Rusnita; Nita Afriani; Yayi Dwina Billianti Susanto; Veronica Y Susilo; Sri Setiyowati; Wirsma Arif Harahap

doi:10.1007/s13139-019-00632-8

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

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

Authors

Aisyah Elliyanti¹, Dewi Rusnita², Nita Afriani³, Yayi Dwina Billianti Susanto⁴, Veronica Y Susilo⁵, Sri Setiyowati⁵, Wirsma Arif Harahap⁶

Affiliations

¹ 1Medical Physics and Radiology Departments, Faculty of Medicine, Universitas Andalas, Kampus Limau Manis, Padang, West Sumatera 25163 Indonesia.
² 2Anatomy Department, Faculty of Medicine, Universitas Andalas, Padang, Indonesia.
³ 3Histology Department, Faculty of Medicine, Universitas Andalas, Padang, Indonesia.
⁴ 4Pathology Anatomy Department, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
⁵ 5The Center of Radioisotopes and Radiopharmaceuticals Technology, Badan Tenaga Nuklir Nasional, Puspitek Serpong, Tangerang Selatan, Indonesia.
⁶ 6Surgery Department, Faculty of Medicine, Universitas Andalas, Padang, Indonesia.

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.