Cerutti Janete M, Latini Flavia R M, Nakabashi Claudia, Delcelo Rosana, Andrade Victor P, Amadei Marcelo João, Maciel Rui M B, Hojaij Flavio C, Hollis Donna, Shoemaker Jennifer, Riggins Gregory J
Department of Neurosurgery, Johns Hopkins University Medical School, Baltimore, Maryland 21231, USA.
Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3311-8. doi: 10.1158/1078-0432.CCR-05-2226.
Fine-needle aspiration (FNA) cytology, a standard method for thyroid nodule diagnosis, cannot distinguish between benign follicular thyroid adenoma (FTA) and malignant follicular thyroid carcinoma (FTC). Previously, using expression profiling, we found that a combination of transcript expression levels from DDIT3, ARG2, C1orf24, and ITM1 distinguished between FTA and FTC. The goal of this study was to determine if antibody markers used alone or in combination could accurately distinguish between a wider variety of benign and malignant thyroid lesions in fixed sections and FNA samples.
Immunohistochemistry was done on 27 FTA, 25 FTC, and 75 other benign and malignant thyroid tissue sections using custom antibodies for chromosome 1 open reading frame 24 (C1orf24) and integral membrane protein 1 (ITM1) and commercial antibodies for DNA damage-inducible transcript 3 (DDIT3) and arginase II (ARG2). FNA samples were also tested using the same antibodies. RNA expression was measured by quantitative PCR in 33 thyroid lesions.
C1orf24 and ITM1 antibodies had an estimated sensitivity of 1.00 for distinguishing FTA from FTC. For the expanded analysis of all lesions studied, ITM1 had an estimated sensitivity of 1.00 for detecting malignancy. Because all four cancer biomarkers did well, producing overlapping confidence intervals, not one best marker was distinguished. Transcript levels also reliably predicted malignancy, but immunohistochemistry had a higher sensitivity. Malignant cells were easily detected in FNA samples using these markers.
We improved this diagnostic test by adding C1orf24 and ITM1 custom antibodies and showing use on a wider variety of thyroid pathology. We recommend that testing of all four cancer biomarkers now be advanced to larger trials. Use of one or more of these antibodies should improve diagnostic accuracy of suspicious thyroid nodules from both tissue sections and FNA samples.
细针穿刺（FNA）细胞学检查是甲状腺结节诊断的标准方法，但无法区分良性滤泡性甲状腺腺瘤（FTA）和恶性滤泡性甲状腺癌（FTC）。此前，通过表达谱分析，我们发现DDIT3、ARG2、C1orf24和ITM1的转录本表达水平组合可区分FTA和FTC。本研究的目的是确定单独或联合使用抗体标志物能否在固定切片和FNA样本中准确区分更多种类的良性和恶性甲状腺病变。
使用针对1号染色体开放阅读框24（C1orf24）和整合膜蛋白1（ITM1）的定制抗体以及针对DNA损伤诱导转录本3（DDIT3）和精氨酸酶II（ARG2）的商业抗体，对27例FTA、25例FTC以及75例其他良性和恶性甲状腺组织切片进行免疫组织化学检测。FNA样本也使用相同抗体进行检测。通过定量PCR测量33例甲状腺病变中的RNA表达。
C1orf24和ITM1抗体区分FTA和FTC的估计灵敏度为1.00。对于所研究的所有病变的扩展分析，ITM1检测恶性肿瘤的估计灵敏度为1.00。由于所有四种癌症生物标志物表现良好，产生重叠的置信区间，因此未区分出最佳标志物。转录本水平也可靠地预测了恶性肿瘤，但免疫组织化学具有更高的灵敏度。使用这些标志物在FNA样本中很容易检测到恶性细胞。
我们通过添加C1orf24和ITM1定制抗体并展示其在更多种类甲状腺病理学中的应用，改进了这种诊断测试。我们建议现在将所有四种癌症生物标志物的检测推进到更大规模的试验。使用这些抗体中的一种或多种应可提高来自组织切片和FNA样本的可疑甲状腺结节的诊断准确性。
