Elliyanti Aisyah, Rusnita Dewi, Afriani Nita, Susanto Yayi Dwina Billianti, Susilo Veronica Y, Setiyowati Sri, Harahap Wirsma Arif
1Medical Physics and Radiology Departments, Faculty of Medicine, Universitas Andalas, Kampus Limau Manis, Padang, West Sumatera 25163 Indonesia.
2Anatomy Department, Faculty of Medicine, Universitas Andalas, Padang, Indonesia.
Nucl Med Mol Imaging. 2020 Feb;54(1):35-42. doi: 10.1007/s13139-019-00632-8. Epub 2020 Jan 3.
This study investigates natrium iodide symporter (NIS) expression in three breast cancer subtypes to predict radioiodine response.
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.
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, = 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 ( = 0.009).
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.
本研究调查三种乳腺癌亚型中碘化钠转运体（NIS）的表达情况，以预测放射性碘反应。
本研究使用了三阴性（TN）、人表皮受体2（HER2+）和腔面A型乳腺癌的冷冻乳腺组织。采用免疫组织化学（IHC）和蛋白质印迹法（WB）分析各亚型中NIS蛋白的表达。年龄、亚型和Ki 67指数等二级数据来自外科肿瘤学家数据库。使用乳腺癌细胞系通过测量细胞增殖来研究放射性碘的作用。
分析的41例乳腺癌样本包括以下亚型：TN、HER2+和腔面A型分别占58%、22%和20%。疾病分期为2A至4A。大多数样本处于3B期。TN、HER2+和腔面A型的Ki 67指数分别为21±12、19±5和7±3。95%的样本在细胞质和/或细胞膜中检测到NIS表达；93%的样本为浸润性乳腺癌。仅20%的样本在细胞膜上显示NIS表达；4个样本为HER2+亚型，另外4个为TN亚型。NIS膜评分与Ki67指数显著正相关，r = 0.04。在88 kDa、50 kDa和27 kDa大小处检测到NIS蛋白表达。MDA-MB 231、SKBR3和MCF7细胞的细胞增殖率平均值分别为81.6±4、10.6±5和15.4±13（P = 0.009）。
乳腺癌细胞中可不同程度地检测到NIS蛋白表达。HER2+亚型最有可能在细胞膜上表达NIS，其次是TN亚型。这表明放射性碘可作为乳腺癌的一种新型辅助治疗方法。
