Dectection of occult mediastinal lymph node mestastases

隐匿性纵隔淋巴结转移的检测

• 批准号: 7014500
• 负责人: MICHAEL Bradley WALLACE
• 金额: $ 31.9万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7014500
• 关键词: biotechnology; clinical research; computed axial tomography; diagnosis design /evaluation; diagnosis quality /standard; endoscopy; fine needle aspiration; gene expression; genetic markers; high throughput technology; histopathology; human subject; lymph node neoplasm; metastasis; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer genetics; nonsmall cell lung cancer; patient oriented research; polymerase chain reaction; positron emission tomography; prognosis

DESCRIPTION (provided by applicant): Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer death in the United States. The presence of metastatic disease in the mediastinal lymph nodes of NSCLC patients has profound prognostic and therapeutic implications. For instance, patients with documented disease in mediastinal lymph nodes are typically not candidates for surgical treatment, and are often treated with a combination of chemotherapy and radiotherapy. Current methods for detection of disease in mediastinal lymph nodes either lack sensitivity (computed tomography, positron emission tomography), or are invasive requiring general anesthesia (mediastinoscopy, thoracoscopy). We believe that endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of mediastinal lymph nodes in combination with real-time RT-PCR has the potential to dramatically improve lung cancer staging. One limitation of EUS-FNA is that it currently relies on cytologic analysis of the specimen. Such an analysis is dependent on a skilled cytopathologist and lacks sensitivity. The identification of genes overexpressed in lung cancer combined with recent advances in molecular biology provides the opportunity to establish a more sensitive, and specific way to analyze EUS-FNA samples. In Section 6c. Preliminary Studies, we present preliminary data that real-time RT-PCR provides the ability to precisely determine the expression levels of lung cancer-associated mRNA, facilitating the sensitive detection of NSCLC. Furthermore, we present evidence of lung cancer-associated gene overexpression in EUS-FNA samples from patients with presumed NSCLC. The hypothesis of the proposed research is that real-time RT-PCR detection of lung cancer cells in EUS-FNA specimens of mediastinal lymph nodes in NSCLC patients is associated with clinical outcome. The successful development and validation of such a molecular diagnostic assay is likely to have a significant clinical impact. In the R21 component of this grant application we will analyze a preliminary cohort of patients and controls so that criteria for the interpretation of test results can be established. In the R33 component of the grant application these criteria will be prospectively evaluated and correlated with clinical outcome in a second, larger cohort of patients.

描述（由申请人提供）： 非小细胞肺癌（NSCLC）是癌症死亡的最常见原因 在美国纵隔转移性疾病的存在 淋巴结转移对NSCLC患者的预后和治疗有重要意义 含义。例如，患有纵隔疾病的患者 淋巴结通常不是手术治疗的候选者，并且常常 接受化疗和放疗的联合治疗。当前方法 对于纵膈淋巴结疾病的检测要么缺乏敏感性 （计算机断层扫描，正电子发射断层扫描），或者是侵入性的，需要 全身麻醉（纵隔镜检查、胸腔镜检查）。我们认为内窥镜检查 超声引导下纵隔淋巴结细针穿刺 与实时RT-PCR相结合有可能显着改善 肺癌分期EUS-FNA的一个局限性是，它目前依赖于 标本的细胞学分析。这种分析依赖于熟练的 细胞病理学家和缺乏敏感性。肺癌高表达基因的筛选及分子生物学研究进展 生物学提供了建立一个更敏感，更具体的 分析EUS-FNA样本的方法。在第6c节中。初步研究，我们提出 初步数据表明，实时RT-PCR提供了精确 确定肺癌相关mRNA的表达水平， 敏感检测NSCLC。此外，我们还提供了肺部 癌症相关基因在EUS-FNA样本中的过度表达 推测为NSCLC。这项研究的假设是， RT-PCR检测纵隔EUS-FNA标本中肺癌细胞 NSCLC患者的淋巴结转移与临床结局相关。的 这种分子诊断测定的成功开发和验证 可能会产生重大的临床影响。在R21组件中， 我们将分析一个初步的患者队列， 控制，以便可以解释测试结果的标准， 确立了习在赠款申请的R33部分中，这些标准将 进行前瞻性评估并与临床结果相关联， 更大的患者群体。