Section of Medical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Thyroid. 2010 Oct;20(10):1067-76. doi: 10.1089/thy.2009.0400.
The accurate diagnosis of thyroid tumors is challenging. Proteomics has emerged as a promising approach for the discovery of molecular diagnostic markers as a potential complement to routine diagnostics.
Protein fractions from 29 frozen thyroid tumor tissue samples (10 papillary carcinomas, 9 follicular carcinomas, and 10 follicular adenomas) as well as from normal thyroid tissue were analyzed by surface enhanced laser desorption/ionization time-of-flight mass spectrometry followed by validation by Western blotting and immunohistochemistry.
A Ca2+ binding protein belonging to the S100 family, S100A6, was differentially expressed between papillary and follicular thyroid tumors. Moreover, two posttranslationally modified forms of S100A6 were observed and verified by liquid chromatography-coupled tandem mass spectrometry. Validation by Western blotting displayed a significantly higher expression of S100A6 in papillary thyroid carcinoma (PTC) in comparison with the other tumor groups or normal tissue (p < 0.05). Immunohistochemical analysis on 98 tumors showed that PTC cases had a significantly stronger cytosolic staining and a larger proportion of stained nuclei than follicular tumors. BRAF gene mutation was not significantly associated with S100A6 protein levels.
This study supports a role of S100A6 in thyroid tumorigenesis and as a potential aid in the discrimination between follicular thyroid tumors and PTC.
甲状腺肿瘤的准确诊断具有挑战性。蛋白质组学已成为发现分子诊断标志物的一种很有前途的方法，可作为常规诊断的补充。
通过表面增强激光解吸/电离飞行时间质谱分析 29 例冷冻甲状腺肿瘤组织样本（10 例乳头状癌、9 例滤泡状癌和 10 例滤泡性腺瘤）以及正常甲状腺组织的蛋白质馏分，然后通过 Western blot 和免疫组织化学进行验证。
钙结合蛋白 S100A6 属于 S100 家族，在甲状腺乳头状和滤泡状肿瘤之间表达不同。此外，观察到两种翻译后修饰形式的 S100A6，并通过液相色谱-串联质谱法进行验证。Western blot 验证显示 S100A6 在甲状腺乳头状癌（PTC）中的表达明显高于其他肿瘤组或正常组织（p < 0.05）。对 98 例肿瘤的免疫组织化学分析表明，PTC 病例的细胞质染色明显更强，染色核的比例也明显高于滤泡状肿瘤。BRAF 基因突变与 S100A6 蛋白水平无显著相关性。
本研究支持 S100A6 在甲状腺肿瘤发生中的作用，并可能有助于区分滤泡状甲状腺肿瘤和 PTC。
