Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM) / University of Campinas, São Paulo, Brazil.
Clin Endocrinol (Oxf). 2011 Aug;75(2):247-54. doi: 10.1111/j.1365-2265.2011.04032.x.
We aimed to investigate the use of NIS mRNA and protein expression as a diagnostic and/or prognostic marker in patients with differentiated thyroid cancer (DTC).
This is a case-control study.
We studied 397 thyroid nodules tissue samples, including 224 papillary thyroid carcinomas (PTCs), 41 follicular carcinomas, 58 nodular goiters, 56 follicular adenomas and 18 normal tissues assembled in a tissue microarray.
NIS protein was identified using a monoclonal antibody that labelled only the follicular cell basolateral membrane of all 397 tissue samples. In addition, NIS mRNA was quantified in 145 DTC patients and 85 PTC cases were screened for BRAF(V600E) mutation.
We found low NIS mRNA expression and low or negative NIS protein expression in most DTC. NIS expression was lower in DTC patients over 45 years old and in tumours larger than 2 cm. There was a tendency for lower NIS expression in advanced stages and patients presenting recurrences. All 13 DTC patients who succumbed to the disease were NIS negative at immunohistochemistry and had very low mRNA expression. NIS expression was lower in PTC presenting BRAF(V600E) mutation. However, neither NIS immunohistochemical analysis nor NIS mRNA quantified expression could identify individuals with poor prognosis.
Our data suggest that NIS expression may help characterize patients' risk and individuals with a poor response to therapy, but is not useful as a diagnostic or prognostic marker, reinforcing the current concept that an appropriate management of DTC patient is the most important and modifiable prognostic factor.
我们旨在研究 NIS mRNA 和蛋白表达作为分化型甲状腺癌(DTC)患者的诊断和/或预后标志物的作用。
这是一项病例对照研究。
我们研究了 397 个甲状腺结节组织样本,包括 224 例甲状腺乳头状癌(PTC)、41 例滤泡状癌、58 例结节性甲状腺肿、56 例滤泡性腺瘤和 18 例正常组织,这些组织都被组装在组织微阵列中。
使用一种仅标记所有 397 个组织样本滤泡细胞基底外侧膜的单克隆抗体来鉴定 NIS 蛋白。此外,我们还在 145 例 DTC 患者中定量了 NIS mRNA,并且对 85 例 PTC 病例进行了 BRAF(V600E)突变筛查。
我们发现大多数 DTC 中 NIS mRNA 表达较低,且 NIS 蛋白表达低或阴性。45 岁以上的 DTC 患者和肿瘤大于 2cm 的患者中 NIS 表达较低。晚期和复发患者的 NIS 表达呈下降趋势。所有 13 例死于该疾病的 DTC 患者的免疫组化均为 NIS 阴性,且 mRNA 表达极低。存在 BRAF(V600E)突变的 PTC 中 NIS 表达较低。然而,无论是 NIS 免疫组化分析还是定量的 NIS mRNA 表达都无法识别预后不良的个体。
我们的数据表明,NIS 表达可能有助于确定患者的风险和对治疗反应不佳的个体,但作为诊断或预后标志物并不有用,这进一步证实了当前的概念,即对 DTC 患者的适当管理是最重要和可改变的预后因素。