Liu Ying Y, Morreau Hans, Kievit Job, Romijn Johannes A, Carrasco Nancy, Smit Johannes W
Department of Endocrinology, C4-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Eur J Endocrinol. 2008 Mar;158(3):375-84. doi: 10.1530/EJE-07-0492.
The microscopic distinction between benign and malignant thyroid lesions in clinical practice is still largely based on conventional histology. This study was performed to evaluate the diagnostic value of galectin-3 (Gal-3), Hector Battifora mesothelial-1 (HBME-1), cytokeratin (CK)-19, CBP P300-interacting transactivator with glutamic acid E- and aspartic acid D-rich C-terminal domain (CITED-1), fibronectin (FN)-1, peroxisome proliferator-activated receptor (PPAR)-gamma, and intracellular sodium/iodide symporter (iNIS) immunostaining in a large panel of thyroid neoplasms. Our study differed from earlier ones with regard to the identification of optimal semiquantitative cut-off levels using receiver operator curve (ROC) analysis and hierarchical cluster analysis.
We used tissue arrays containing 177 thyroid tissues: 100 benign tissues (including normal thyroid, Graves disease, multinodular goiter, and follicular adenoma (FA)) and 77 thyroid carcinomas (including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, and follicular variant of PTC (FVPTC)). Antibody staining was scored semiquantitatively based on the ROC analyses and with hierarchical cluster analysis.
In general, we found overexpression of FN-1, CITED-1, Gal-3, CK-19, HBME-1, and iNIS in malignant thyroid lesions. Gal-3, FN-1, and iNIS had the highest accuracy in the differential diagnosis of follicular lesions. A panel of Gal-3, FN-1, and iNIS, identified by hierarchical cluster analysis, had a 98% accuracy to differentiate between FA and malignant thyroid lesions. In addition, HBME-1 was found to be useful in the differentiation between FA and FVPTC (accuracy 88%).
We conclude that identifying optimal antibody panels with cluster analysis increases the diagnostic value in the differential diagnosis of thyroid neoplasms, the combination of FN-1, Gal-3, and iNIS having the best accuracy (98%).
在临床实践中,甲状腺良恶性病变的微观区分在很大程度上仍基于传统组织学。本研究旨在评估半乳凝素-3(Gal-3)、赫克托·巴蒂福拉间皮素-1(HBME-1)、细胞角蛋白(CK)-19、含谷氨酸E和天冬氨酸D丰富C末端结构域的CBP P300相互作用反式激活因子(CITED-1)、纤连蛋白(FN)-1、过氧化物酶体增殖物激活受体(PPAR)-γ以及细胞内钠/碘同向转运体(iNIS)免疫染色在一大组甲状腺肿瘤中的诊断价值。我们的研究在使用受试者操作特征曲线(ROC)分析和层次聚类分析确定最佳半定量截断水平方面与早期研究不同。
我们使用了包含177个甲状腺组织的组织芯片:100个良性组织(包括正常甲状腺、格雷夫斯病、多结节性甲状腺肿和滤泡性腺瘤(FA))和77个甲状腺癌(包括乳头状甲状腺癌(PTC)、滤泡状甲状腺癌和PTC滤泡变体(FVPTC))。基于ROC分析和层次聚类分析对抗体染色进行半定量评分。
总体而言,我们发现FN-1、CITED-1、Gal-3、CK-19、HBME-1和iNIS在恶性甲状腺病变中过表达。Gal-3、FN-1和iNIS在滤泡性病变的鉴别诊断中准确性最高。通过层次聚类分析确定的Gal-3、FN-1和iNIS组合在区分FA和恶性甲状腺病变方面的准确率为98%。此外,发现HBME-1在区分FA和FVPTC方面有用(准确率88%)。
我们得出结论,通过聚类分析确定最佳抗体组合可提高甲状腺肿瘤鉴别诊断的价值,FN-1、Gal-3和iNIS的组合准确率最高(98%)。