Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain.
Hum Pathol. 2012 Jul;43(7):1103-12. doi: 10.1016/j.humpath.2011.08.022. Epub 2011 Dec 29.
Thyroid paraganglioma is a rare disorder that sometimes poses problems in differential diagnosis with medullary thyroid carcinoma. So far, differential diagnosis is solved with the help of some markers that are frequently expressed in medullary thyroid carcinoma (thyroid transcription factor 1, calcitonin, and carcinoembryonic antigen). However, some of these markers are not absolutely specific of medullary thyroid carcinoma and may be expressed in other tumors. Here we report 3 new cases of thyroid paraganglioma and describe our strategy to design a diagnostic immunohistochemical battery. First, we performed a comparative analysis of the expression profile of head and neck paragangliomas and medullary thyroid carcinoma, obtained after complementary DNA array analysis of 2 series of fresh-frozen samples of paragangliomas and medullary thyroid carcinoma, respectively. Seven biomarkers showing differential expression were selected (nicotinamide adenine dinucleotide dehydrogenase 1 alpha subcomplex, 4-like 2, NDUFA4L2; cytochrome c oxidase subunit IV isoform 2; vesicular monoamine transporter 2; calcitonin gene-related protein/calcitonin; carcinoembryonic antigen; and thyroid transcription factor 1) for immunohistochemical analysis. Two tissue microarrays were constructed from 2 different series of paraffin-embedded samples of paragangliomas and medullary thyroid carcinoma. We provide a classifying rule for differential diagnosis that combines negativity or low staining for calcitonin gene-related protein (histologic score, <10) or calcitonin (histologic score, <50) together with positivity of any of NADH dehydrogenase 1 alpha subcomplex, 4-like 2; cytochrome c oxidase subunit IV isoform 2; or vesicular monoamine transporter 2 to predict paragangliomas, showing a prediction error of 0%. Finally, the immunohistochemical battery was checked in paraffin-embedded blocks from 4 examples of thyroid paraganglioma (1 previously reported case and 3 new cases), showing also a prediction error of 0%. Our results suggest that the comparative expression profile, obtained by complementary DNA arrays, seems to be a good tool to design immunohistochemical batteries used in differential diagnosis.
甲状腺副神经节瘤是一种罕见的疾病，有时在与甲状腺髓样癌的鉴别诊断中存在问题。到目前为止，鉴别诊断是借助于一些在甲状腺髓样癌中经常表达的标志物来解决的（甲状腺转录因子 1、降钙素和癌胚抗原）。然而，这些标志物中的一些并不是甲状腺髓样癌的绝对特异性标志物，也可能在其他肿瘤中表达。本文报告了 3 例甲状腺副神经节瘤新病例，并描述了我们设计诊断免疫组织化学组合的策略。首先，我们通过对 2 组分别为副神经节瘤和甲状腺髓样癌的新鲜冷冻样本进行 cDNA 阵列分析，对头颈部副神经节瘤和甲状腺髓样癌的表达谱进行了比较分析。选择了 7 种显示差异表达的生物标志物（烟酰胺腺嘌呤二核苷酸脱氢酶 1α亚基，4 样 2，NDUFA4L2；细胞色素 c 氧化酶亚基 IV 同工型 2；囊泡单胺转运体 2；降钙素基因相关蛋白/降钙素；癌胚抗原；和甲状腺转录因子 1）进行免疫组织化学分析。从 2 组不同的副神经节瘤和甲状腺髓样癌石蜡包埋样本中构建了 2 个组织微阵列。我们提供了一种用于鉴别诊断的分类规则，将降钙素基因相关蛋白（组织学评分<10）或降钙素（组织学评分<50）的阴性或低染色与 NADH 脱氢酶 1α亚基、4 样 2；细胞色素 c 氧化酶亚基 IV 同工型 2；或囊泡单胺转运体 2 的任何一种阳性相结合，预测副神经节瘤，预测错误率为 0%。最后，对 4 例甲状腺副神经节瘤（1 例既往报道病例和 3 例新病例）的石蜡包埋块进行了免疫组织化学检测，预测错误率也为 0%。我们的结果表明，通过 cDNA 阵列获得的比较表达谱似乎是设计用于鉴别诊断的免疫组织化学组合的良好工具。
