Molecular Staging Of Lymph Nodes In Head And Neck Cancer

描述（由申请人提供）：头颈部鳞状细胞癌（SCCHN）经常转移到区域淋巴结，这是疾病预后和结局的最佳预测因素。颈部淋巴结的准确分期对于最佳的患者管理至关重要，但目前的临床方法是不够的，并且在许多患者中误诊了颈部淋巴结转移的存在或不存在。因此，目前的标准治疗，选择性颈清扫术，可能代表超过50%的临床肿瘤阴性患者的过度治疗。前哨淋巴结（SLN）活检可能解决这个问题，目前正在进行多中心验证试验。这种方法的一个问题是目前缺乏高度准确、快速（术中）的测定来评估SLN。冷冻切片分析的灵敏度仅为60-80%，当最终组织学检测到转移性疾病时，由于冷冻切片分析而导致的假阴性通常会导致二次手术。由于技术难度增加、二次手术和麻醉剂的发病率、诊断不确定性引起的焦虑和成本增加，对这种SLN活检颈部的再手术可能不受患者和外科医生的欢迎。此外，7-10%的病理学肿瘤阴性患者表现出肿瘤复发，可能表明存在病理学隐匿性疾病。我们假设定量RT-PCR（qRT-PCR）可以克服这些问题，并可以在术中时间范围内提供准确，明确的颈部分期。在初步研究中，我们已经确定了SCCHN中qRT-PCR的突出标志物。我们还开发了在临床环境中促进快速、内部控制和自动化qRT-PCR的方法。在当前的提案中，我们将证明我们的全自动qRT-PCR检测可以优化用于术中时间范围，并且可以以标准化和可重现的方式进行。这些检测应该被证明是SCCHN患者淋巴结分期的有用工具。

DESCRIPTION (provided by applicant): Squamous cell carcinoma of the head and neck (SCCHN) frequently metastasizes to the regional lymphatics and this is the best predictor of disease prognosis and outcome. Accurate staging of lymph nodes in the neck is essential to optimal patient management, but current clinical methods are inadequate, and misdiagnose the presence or absence of cervical nodal metastasis in many patients. Consequently, the current standard of care, elective neck dissection, may represent overtreatment of over 50% of clinically tumor-negative patients. Sentinel lymph node (SLN) biopsy may obviate this problem, and is currently undergoing a multi-center validation trial. One problem with this approach is the current lack of a highly accurate, rapid (intraoperative) assay to assess the SLN. Frozen section analysis is only 60-80% sensitive, and false negatives due to frozen section analysis would frequently result in second procedures when final histology detects metastatic disease. Re-operation on such SLN biopsied necks is likely to be poorly received by both patients and surgeons, due to increased technical difficulty, morbidity of a second surgery and anesthetic, anxiety due to diagnostic uncertainty and increased costs. In addition, 7-10% of pathologically tumor negative patients manifest tumor recurrence, possibly indicating the presence of pathologically occult disease. We hypothesize that quantitative RT-PCR (qRT-PCR) can overcome these problems and can provide accurate, definitive staging of the neck in an intraoperative time frame. In preliminary studies, we have identified outstanding markers for qRT-PCR in SCCHN. We have also developed methods to facilitate rapid, internally controlled and automated qRT-PCR in a clinical setting. In the current proposal, we will demonstrate that our fully automated qRT-PCR assays can be optimized for use in an intraoperative time frame, and that they can be performed in a standardized and reproducible manner. These assays should prove to be useful tools for staging of lymph nodes from SCCHN patients.