Preoperative and follow-up tests for thyroid tumors

描述（由申请人提供）：我们的长期目标是开发一种更准确的测试方法，可以在术前区分良性和恶性甲状腺结节。目前，细针穿刺（FNA）细胞学是评估甲状腺结节的最佳非手术诊断工具。然而，大约30%的结节被归类为可疑结节。由于目前的方法是基于形态学特征，未能提高敏感性和特异性，因此仍然是临床常见的问题，特别是对病理学家的挑战。为了解决这个问题，我们之前对滤泡性甲状腺腺瘤（FTA）和滤泡性甲状腺癌（FTC）进行了基因表达谱分析。该分析和随后的分析显示，四种新的标记物（DDIT3、ARG2、C1orf24和ITM1）在两种肿瘤之间存在差异，表达水平的线性组合将FTC与FTA区分开来，估计预测准确率为0.83。在一组独立的FTA和FTC石蜡包埋切片中，使用市售的DDIT3和ARG2抗体进行进一步验证。每种抗体的敏感性和特异性分别为85%和91%。联合使用这两种抗体并没有提高估计值。我们定制了针对C1or24和ITM1的抗体，并在上述的FTA和FTC章节中进行了测试。我们达到了100%的灵敏度。此外，这些新的标记物可以可靠地将其他甲状腺病变划分为良性或恶性。我们的假设是，基因表达谱将找到新的诊断标记，可以提高测试的特异性。我们将使用基因表达序列分析（SAGE）来分析最初被误诊为恶性的Hurthle细胞腺瘤，从而提高术前诊断测试的特异性。我们的下一个目标是开发一种可以常规用作FNA细胞学辅助的测试。为了实现这一目标，我们建议在本申请的R33期评估抗体和定量RT-PCR检测诊断甲状腺结节的有效性。为了评估这两种测试的准确性和可行性，将这些分析结果与最终组织学进行比较。开发一种创新的、更准确的甲状腺结节术前诊断测试，不仅会在癌症诊断方面取得进展，而且还会改善治疗决策，同时降低长期健康成本。

DESCRIPTION (provided by applicant): Our long term goal is to develop a more accurate test that can preoperatively distinguish a benign from a malignant thyroid nodule. Currently, fine-needle aspiration (FNA) cytology is the best non-surgical diagnostic tool for evaluating a thyroid nodule. However, approximately 30% of all nodules are classified as suspicious. Because the current method is based on morphological features, and fails to improve the sensitivity and specificity, it remains a frequent clinical problem with challenges in particular to the pathologist. To address this problem, we previously performed gene expression profiling both a follicular thyroid adenoma (FTA), and a follicular thyroid carcinoma (FTC). This profiling and subsequent analysis revealed that four novel markers (DDIT3, ARG2, C1orf24 and ITM1) differed between the two tumors and a linear combination of expression levels distinguished FTC from FTA with an estimated predictive accuracy of 0.83. Commercially available antibodies for DDIT3 and ARG2 were used for further validation in an independent set of FTA and FTC paraffin-embedded sections. Sensitivity and specificity were 85% and 91% respectively for each antibody. Using the two antibodies in combination did not improve the estimates. We custom produced antibodies for C1or24 and ITM1 and tested them in the aforementioned set of FTA and FTC sections. We achieved a sensitivity of 100%. Furthermore, these novel markers can reliably classify other thyroid lesions into benign or malignant classes. Our hypothesis is that gene expression profiling will locate novel diagnostic markers that can improve the specificity of the test. We will use Serial Analysis of Gene Expression (SAGE), to profile Hurthle cell adenoma which was originally misclassified as malignant and, therefore, predicted to improve the specificity of preoperative diagnosis test. Our next goal is to develop a test that can be routinely used as an adjuvant with FNA cytology. To achieve this goal, we propose in R33 phase of this application to evaluate the effectiveness of both antibody and quantitative RT-PCR tests to diagnose thyroid nodules. To assess the accuracy and feasibility of both tests, the results from these analyses will be compared with final histology. The development of an innovative and more accurate preoperative diagnostic test for evaluating thyroid nodules will not only result in progress in cancer diagnosis but will also improve treatment decisions while reducing long-term health costs.