Erickson Lori A, Vrana Julie A, Theis Jason, Rivera Michael, Lloyd Ricardo V, McPhail Ellen, Zhang Jun
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55901, USA.
Endocr Pathol. 2015 Dec;26(4):291-5. doi: 10.1007/s12022-015-9390-7.
Amyloid is a characteristic histologic feature in medullary thyroid carcinomas (MTC). We utilized a novel mass spectrometry-based proteomic analysis to determine if we could identify specific proteins associated with amyloid in MTC. We studied 9 MTC (1 multiple endocrine neoplasia type 2A, 1 familial MTC, and 7 sporadic). Laser microdissection was utilized to sample the amyloid which was then trypsin digested and evaluated by liquid chromatography electrospray tandem MS (LC-MS/MS) which identified the presence of amyloidogenic proteins in all cases of MTC. High levels of calcitonin were identified in all 9 cases of MTC. Secretogranin-1 was identified in 6 of 9 MTC. Calcitonin gene-related peptide was identified in 4 of 9 cases of MTC. LC-MS/MS proteomic analysis provides a rapid, highly specific, and sensitive method for identification of the specific type of amyloid in these endocrine tumors. This approach may allow classification of different forms of endocrine amyloid present in neuroendocrine tumors.
淀粉样蛋白是甲状腺髓样癌（MTC）的一个特征性组织学特征。我们利用一种基于质谱的新型蛋白质组学分析方法，来确定是否能够识别出与MTC中淀粉样蛋白相关的特定蛋白质。我们研究了9例MTC（1例2A型多发性内分泌腺瘤病、1例家族性MTC和7例散发性MTC）。采用激光显微切割技术对淀粉样蛋白进行取样，随后用胰蛋白酶消化，并通过液相色谱电喷雾串联质谱（LC-MS/MS）进行评估，结果在所有MTC病例中均鉴定出了淀粉样蛋白生成蛋白。在所有9例MTC中均检测到高水平的降钙素。在9例MTC中的6例中鉴定出分泌粒蛋白-1。在9例MTC中的4例中鉴定出降钙素基因相关肽。LC-MS/MS蛋白质组学分析为识别这些内分泌肿瘤中特定类型的淀粉样蛋白提供了一种快速、高度特异且灵敏的方法。这种方法可能有助于对神经内分泌肿瘤中存在的不同形式的内分泌淀粉样蛋白进行分类。
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