Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive H 3625, Stanford, CA 94305-5655, USA.
J Neurooncol. 2010 Feb;96(3):331-6. doi: 10.1007/s11060-009-9971-8. Epub 2009 Jul 19.
Breast cancer brain metastases are on the rise and their treatment is hampered by the limited entry and efficacy of anticancer drugs in this sanctuary. The sodium iodide symporter, NIS, actively transports iodide across the plasma membrane and is exploited clinically to deliver radioactive iodide into cells. As in thyroid cancers, NIS is expressed in many breast cancers including primary and metastatic tumors. In this study NIS expression was analyzed for the first time in 28 cases of breast cancer brain metastases using a polyclonal anti-NIS antibody directed against the terminal C-peptide of human NIS gene and immunohistochemical methods. Twenty-five tumors (84%) in this retrospective series were estrogen/progesterone receptor-negative and 15 (53.6%) were HER2+. Overall 21 (75%) cases and 80% of HER2 positive metastases were NIS positive. While the predominant pattern of NIS immunoreactivity is intracellular, plasma membrane immunopositivity was detected at least focally in 23.8% of NIS-positive samples. Altogether, these findings indicate that NIS expression is prevalent in breast cancer brain metastases and could have a therapeutic role via the delivery of radioactive iodide and selective ablation of tumor cells.
乳腺癌脑转移正在增加,由于抗癌药物在这个避难所中的有限进入和疗效,其治疗受到阻碍。钠碘转运体(NIS)可主动将碘跨膜转运,并且在临床上被用于将放射性碘递送至细胞中。与甲状腺癌一样,许多乳腺癌包括原发性和转移性肿瘤中均表达 NIS。在这项研究中,首次使用针对人 NIS 基因末端 C 肽的多克隆抗 NIS 抗体和免疫组织化学方法,分析了 28 例乳腺癌脑转移瘤中的 NIS 表达。在这个回顾性系列中,25 例肿瘤(84%)雌激素/孕激素受体阴性,15 例(53.6%)HER2+。总体而言,21 例(75%)病例和 80%的 HER2 阳性转移瘤为 NIS 阳性。虽然 NIS 免疫反应的主要模式是细胞内,但在至少 23.8%的 NIS 阳性样本中检测到了细胞膜免疫阳性。总之,这些发现表明 NIS 表达在乳腺癌脑转移瘤中很常见,并且可以通过放射性碘的递送和肿瘤细胞的选择性消融发挥治疗作用。