Jin Long, Lloyd Ricardo V, Nassar Aziza, Lappinga Paul J, Sebo Thomas J, Swartz Kathy, Seys Amber R, Erickson-Johnson Michele R, Roth Christopher W, Evers Barbara R, Oliveira Andre M, Zhang Jun
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Diagn Mol Pathol. 2011 Jun;20(2):71-80. doi: 10.1097/PDM.0b013e3181ed784d.
The distinction between benign and malignant thyroid tumors in some cytological and histological specimens remains challenging. The aim of this study was to evaluate the use of High Mobility Group A2 (HMGA2) mRNA expression to distinguish benign from malignant thyroid tumors in cytological and histological specimens. RNA samples from 170 thyroid formalin-fixed paraffin-embedded (FFPE) tissues and 226 fine needle aspiration (FNA) specimens were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The FFPE tissues included 34 follicular adenomas, 10 Hürthle cell adenomas (HA), 6 hyperplastic nodules, 4 atypical adenomas, 44 classic papillary thyroid carcinomas (PTC), 29 follicular variant of PTC, 23 follicular thyroid carcinomas, 17 Hürthle cell carcinomas (HC), and 3 anaplastic thyroid carcinomas. The FNA specimens included 55 follicular adenomas, 34 HA, 20 hyperplastic nodules, 8 Hashimoto thyroiditis, 32 PTC, 24 follicular variant of PTC, 30 follicular thyroid carcinomas, 21 HC, and 2 anaplastic thyroid carcinomas. HMGA2 mRNA levels were expressed as relative fold change after normalizing with a calibrator. HMGA2 expression in thyroid carcinomas (16.8-fold for FFPE and 18.2-fold for FNA) was significantly higher than in benign lesions (0.8-fold for FFPE and 0.8-fold for FNA). HMGA2 expression in HC was relatively low (1.8-fold for FFPE and 8.5-fold for FNA) compared with the other types of carcinomas. HMGA2 expression values of 4.5-fold and 5.9-fold were used as cutoff points for FFPE and FNA (excluding HA and HC), respectively, to separate benign and malignant thyroid tumors, with 97.5% clinical specificity and 79.8% sensitivity for FFPE, and 95.2% clinical specificity and 88.6% sensitivity for the FNA specimens. Conventional RT-PCR supported the qRT-PCR results. Detection of HMGA2 mRNA expression by qRT-PCR may be a useful tool to assist in the diagnosis of well-differentiated thyroid carcinomas. The 1-step qRT-PCR method is a sensitive, accurate, and reliable technique for gene expression analysis of thyroid tumors.
在一些细胞学和组织学标本中，区分甲状腺良性和恶性肿瘤仍然具有挑战性。本研究的目的是评估高迁移率族蛋白A2（HMGA2）mRNA表达在细胞学和组织学标本中区分甲状腺良性和恶性肿瘤的作用。通过定量逆转录聚合酶链反应（qRT-PCR）分析了170份甲状腺福尔马林固定石蜡包埋（FFPE）组织和226份细针穿刺（FNA）标本的RNA样本。FFPE组织包括34例滤泡性腺瘤、10例许特莱细胞腺瘤（HA）、6例增生性结节、4例非典型腺瘤、44例经典乳头状甲状腺癌（PTC）、29例PTC滤泡变体、23例滤泡性甲状腺癌、17例许特莱细胞癌（HC）和3例间变性甲状腺癌。FNA标本包括55例滤泡性腺瘤项、34例HA、20例增生性结节、8例桥本甲状腺炎、32例PTC、24例PTC滤泡变体、30例滤泡性甲状腺癌、21例HC和2例间变性甲状腺癌。HMGA2 mRNA水平以与校准物归一化后的相对倍数变化表示。甲状腺癌中HMGA2的表达（FFPE为16.8倍，FNA为18.2倍）显著高于良性病变（FFPE为0.8倍，FNA为0.8倍）。与其他类型的癌相比，HC中HMGA2的表达相对较低（FFPE为1.8倍，FNA为8.5倍）。HMGA2表达值4.5倍和5.9倍分别用作FFPE和FNA（不包括HA和HC）区分甲状腺良性和恶性肿瘤的截断点，FFPE的临床特异性为97.5%，敏感性为79.8%，FNA标本的临床特异性为95.2%，敏感性为88.6%。常规RT-PCR支持qRT-PCR结果。通过qRT-PCR检测HMGA2 mRNA表达可能是辅助诊断高分化甲状腺癌的有用工具。一步qRT-PCR方法是一种用于甲状腺肿瘤基因表达分析的灵敏、准确和可靠的技术。
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