Tavares Catarina, Coelho Maria João, Eloy Catarina, Melo Miguel, da Rocha Adriana Gaspar, Pestana Ana, Batista Rui, Ferreira Luciana Bueno, Rios Elisabete, Selmi-Ruby Samia, Cavadas Bruno, Pereira Luísa, Sobrinho Simões Manuel, Soares Paula
Instituto de Investigação e Inovação em Saúde (i3S)Porto, Portugal.
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP)Porto, Portugal.
Endocr Connect. 2018 Jan;7(1):78-90. doi: 10.1530/EC-17-0302.
Thyroid cancer therapy is based on surgery followed by radioiodine treatment. The incorporation of radioiodine by cancer cells is mediated by sodium iodide symporter (NIS) (codified by the gene), that is functional only when targeted to the cell membrane. We aimed to evaluate if NIS expression in thyroid primary tumors would be helpful in predicting tumor behavior, response to therapy and prognosis. NIS expression was addressed by qPCR and immunohistochemistry. In order to validate our data, we also studied expression on 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database. In our series, expression was lower in carcinomas with vascular invasion and with extrathyroidal extension and in those harboring V600E mutation. Analysis of expression from TCGA database confirmed our results. Furthermore, it showed that larger tumors, with locoregional recurrences and/or distant metastases or harboring , and/or promoter (p) mutations presented significantly less expression. Regarding immunohistochemistry, 12/211 of the cases demonstrated NIS in the membrane of tumor cells, those cases showed variable outcomes concerning therapy success, prognosis and all but one were wild type for , and p mutations. mRNA lower expression is associated with features of aggressiveness and with key genetic alterations involving , and p. Mutations in these genes seem to decrease protein expression and its targeting to the cell membrane. mRNA expression is more informative than NIS immunohistochemical expression regarding tumor aggressiveness and prognostic features.
甲状腺癌的治疗基于手术,随后进行放射性碘治疗。癌细胞对放射性碘的摄取由碘化钠同向转运体(NIS)(由该基因编码)介导,NIS只有靶向细胞膜时才具有功能。我们旨在评估甲状腺原发性肿瘤中NIS的表达是否有助于预测肿瘤行为、对治疗的反应和预后。通过定量聚合酶链反应(qPCR)和免疫组织化学检测NIS的表达。为了验证我们的数据,我们还研究了癌症基因组图谱(TCGA)数据库中378例原发性甲状腺乳头状癌的表达情况。在我们的研究系列中,在伴有血管侵犯、甲状腺外侵犯以及携带V600E突变的癌组织中,表达较低。对TCGA数据库中表达的分析证实了我们的结果。此外,分析表明,更大的肿瘤、伴有局部复发和/或远处转移的肿瘤或携带、和/或启动子(p)突变的肿瘤,其表达明显较低。关于免疫组织化学,211例病例中有12例在肿瘤细胞膜上显示NIS,这些病例在治疗成功率、预后方面表现出不同的结果,除1例之外,所有病例的、和p突变均为野生型。mRNA低表达与侵袭性特征以及涉及、和p的关键基因改变有关。这些基因的突变似乎会降低蛋白质表达及其向细胞膜的靶向定位。就肿瘤侵袭性和预后特征而言,mRNA表达比NIS免疫组织化学表达更具信息价值。