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胚胎形态发生素Nodal在分化型甲状腺癌中的表达:组织芯片免疫组化检测及癌症基因组图谱数据分析

Expression of the embryonic morphogen Nodal in differentiated thyroid carcinomas: Immunohistochemistry assay in tissue microarray and The Cancer Genome Atlas data analysis.

作者信息

Chai Young Jun, Kim Young A, Jee Hyeon-Gun, Yi Jin Wook, Jang Bo Gun, Lee Kyu Eun, Park Young Joo, Youn Yeo-Kyu

机构信息

Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Korea.

Department of Pathology, Seoul National University Boramae Medical Center, Seoul, Korea.

出版信息

Surgery. 2014 Dec;156(6):1559-67; discussion 1567-8. doi: 10.1016/j.surg.2014.08.050. Epub 2014 Nov 11.

DOI:10.1016/j.surg.2014.08.050
PMID:25456955
Abstract

BACKGROUND

Nodal, an embryonic morphogen, plays a role in tumorigenesis of melanoma, breast, and prostate cancer; however, its role in thyroid carcinoma is unknown. We examined Nodal expression in thyroid tumors by immunohistochemistry assay and The Cancer Genome Atlas (TCGA) analysis.

METHODS

An immunohistochemistry assay was performed in a tissue microarray comprising 128 classic papillary thyroid carcinomas (PTC), 58 follicular thyroid carcinomas (FTC), 19 follicular variants of PTC (FVPTC), 57 follicular adenomas (FA), 54 adenomatous goiters (AG), and 5 normal thyroid tissues. The TCGA database was examined to evaluate the expression of Nodal mRNA in normal thyroid and PTC.

RESULTS

The proportion of tumors showing negative Nodal expression in PTC, FTC, FVPTC, FA, and AG was 0%, 1.7%, 0%, 14%, and 41%, respectively. For the diagnosis of malignant tumors, the sensitivity, specificity, positive predictive value, and negative predictive value of positive Nodal staining was 99%, 27%, 72%, and 97%, respectively. High Nodal expression was associated with older age and BRAF mutation in PTC. TCGA analysis revealed PTC had greater Nodal mRNA expression than normal thyroid (P = .012).

CONCLUSION

Nodal staining might be useful "rule-out test" for the diagnosis of malignant thyroid tumor. Nodal may be associated with the tumorigenesis of thyroid malignancy.

摘要

背景

Nodal是一种胚胎形态发生素,在黑色素瘤、乳腺癌和前列腺癌的肿瘤发生中起作用;然而,其在甲状腺癌中的作用尚不清楚。我们通过免疫组织化学分析和癌症基因组图谱(TCGA)分析检测了甲状腺肿瘤中Nodal的表达。

方法

在一个组织微阵列中进行免疫组织化学分析,该微阵列包含128例经典乳头状甲状腺癌(PTC)、58例滤泡状甲状腺癌(FTC)、19例PTC滤泡变体(FVPTC)、57例滤泡性腺瘤(FA)、54例腺瘤性甲状腺肿(AG)和5例正常甲状腺组织。检测TCGA数据库以评估正常甲状腺和PTC中Nodal mRNA的表达。

结果

PTC、FTC、FVPTC、FA和AG中Nodal表达阴性的肿瘤比例分别为0%、1.7%、0%、14%和41%。对于恶性肿瘤的诊断,Nodal染色阳性的敏感性、特异性、阳性预测值和阴性预测值分别为99%、27%、72%和97%。PTC中Nodal高表达与年龄较大和BRAF突变相关。TCGA分析显示PTC的Nodal mRNA表达高于正常甲状腺(P = 0.012)。

结论

Nodal染色可能是诊断甲状腺恶性肿瘤的有用“排除试验”。Nodal可能与甲状腺恶性肿瘤的发生有关。

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