Dectection of occult mediastinal lymph node mestastases

隐匿性纵隔淋巴结转移的检测

• 批准号: 6894623
• 负责人: MICHAEL Bradley WALLACE
• 金额: $ 31.88万
• 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/6894623
• 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)是最常见的癌症死亡原因 在美国。纵隔转移性病变的存在 非小细胞肺癌患者的淋巴转移具有深远的预后和治疗意义 这意味着什么。例如，有记录的纵隔疾病患者 淋巴结通常不适合手术治疗，而且通常是 用化疗和放射治疗相结合的方法治疗。当前的方法 对于纵隔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)，或侵入性要求 全身麻醉(纵隔镜、胸腔镜术)。我们认为内窥镜检查 超声引导下纵隔淋巴结细针吸取(EUS-FNA) 与实时RT-PCR相结合，有可能显著提高 肺癌分期。EUS-FNA的一个限制是它目前依赖于 标本的细胞学分析。这样的分析依赖于一个熟练的 细胞病理学家，缺乏敏感度。肺癌中高表达基因的鉴定及分子生物学研究进展 生物学提供了建立更敏感、更特异的 分析EUS-FNA样本的方法。在第6c条中。初步研究，我们呈现 初步数据表明，实时RT-PCR提供了精确 测定肺癌相关基因的表达水平，促进 非小细胞肺癌的敏感检测。此外，我们提出了肺脏的证据 卵巢癌患者EUS-FNA标本中肿瘤相关基因的过度表达 推测为非小细胞肺癌。拟议研究的假设是实时 RT-PCR检测纵隔EUS-FNA标本中的肺癌细胞 非小细胞肺癌患者的淋巴转移与临床预后有关。这个 这种分子诊断分析的成功开发和验证是 可能会对临床产生重大影响。在此的R21组件中 批准申请我们将分析初步的患者队列和 控件，以便解释测试结果的标准可以 已经成立了。在赠款申请的R33部分中，这些标准将 在一秒钟内进行前瞻性评估并与临床结果相关联， 更大的患者队列。