HTERT GENE EXPRESSION IN SUSPICIOUS THYROID FNA SAMPLES

可疑甲状腺 FNA 样本中的 HTERT 基因表达

• 批准号: 6124691
• 负责人: MARTHA Allen ZEIGER
• 金额: $ 12.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6124691
• 关键词: RNA directed DNA polymerase; clinical research; clinical trials; diagnosis design /evaluation; fine needle aspiration; gene expression; human subject; longitudinal human study; neoplasm /cancer diagnosis; neoplasm /cancer genetics; polymerase chain reaction; telomerase; thyroid neoplasm

DESCRIPTION: (adapted from the investigator's abstract) Although fine needle aspiration (FNA) of thyroid nodules is the most sensitive and specific method for the detection of malignancy, a majority of patients who require surgery for a suspicion of malignancy have only an indeterminate or suspicious diagnosis cytologically. Because the distinction between benign and malignant cannot be made pre- or intra-operatively in these cases, patients with benign lesions may undergo more extensive surgery than necessary and conversely, patients with carcinoma, less than adequate initial surgery. Although various genetic alterations have been documented in thyroid neoplasms and are believed to be associated with their tumorigenesis and malignant progression, no specific alteration can reliably distinguish benign from malignant lesions. Relevant to this, the enzyme telomerase, has been reported to be reactivated in almost all malignant neoplasms, whereas its expression is repressed in almost all normal cells. Recently, the catalytic component of telomerase, human telomerase reverse transcriptase (hTERT), has been cloned and sequence. She has developed a detection method for hTERT gene expression using reverse transcriptase polymerase chain reaction (RT-PCR) and examined its expression in both thyroid nodules and FNAs. She has found that its expression correlates with telomerase enzyme activity and that the detection of hTERT is a more sensitive assay than telomerase activity. She also has found gene expression to be positive in indeterminate FNA samples from 13/14 malignant tumors, and negative in 9/10 benign tumors. The detection of hTERT gene expression in thyroid FNA samples therefore holds tremendouse pomise as a diagnostic marker of thyroid malignancy. Its application to suspicious thyroid FNA samples could dramatically alter the surgical management of patients with these lesions. Because of this, she proposes to conduct a blinded prospective multi-institutional study, examining 240 FNA samples from suspicious thyroid lesions for hTERT expression in order to estimate its sensitivity and specificity and in order to determine whether it can serve as an accurate marker of malignancy in the differential diagnosis of the suspicious thyroid nodule.

描述：（改编自研究者摘要）虽然细针 甲状腺结节穿刺活检（FNA）是最敏感和特异的方法 对于恶性肿瘤的检测，大多数需要手术的患者 恶性肿瘤的怀疑只有不确定或可疑的诊断 细胞学上因为良性和恶性之间的区别不能被 在这些情况下，术前或术中进行检查，良性病变患者可能 接受比必要的更广泛的手术，相反， 癌症，不足以初步手术。 尽管在甲状腺肿瘤中有各种遗传改变的记录， 并且被认为与它们的肿瘤发生和恶性肿瘤有关 进展，没有特异性改变可以可靠地区分良性和 恶性病变与此相关的是端粒酶， 在几乎所有的恶性肿瘤中被重新激活，而其表达在 在几乎所有正常细胞中都受到抑制。最近， 端粒酶，人端粒酶逆转录酶（hTERT），已被克隆， 顺序她开发了一种检测hTERT基因表达的方法， 逆转录聚合酶链反应（RT-PCR），并检测其 在甲状腺结节和FNA中表达。她发现它的表达 与端粒酶活性相关，hTERT的检测是一种有效的方法。 比端粒酶活性更敏感。她还发现吉恩 在13/14例恶性肿瘤的不确定FNA样本中表达为阳性 9/10例良性肿瘤为阴性。hTERT基因的检测 因此，在甲状腺FNA样本中的表达， 甲状腺恶性肿瘤的诊断标志物。它在可疑甲状腺中的应用 FNA样本可以显著改变患者的手术治疗， 这些损伤。正因为如此，她建议进行一个盲目的前瞻性 一项多机构研究，检查了来自可疑甲状腺的240份FNA样本 hTERT表达的病变，以估计其敏感性， 特异性，以确定它是否可以作为一个准确的 恶性肿瘤标志物在甲状腺可疑病变鉴别诊断中的应用 结节。