Ultrastaging of Early Colon Cancer

描述(由申请人提供)：二期结肠癌(CC)手术切除后20-30%的复发率表明结节采样不足和/或组织学评估不够敏感和特异性。我们前哨淋巴结(SN)研究(CA 90484)的初步结果显示，常规采样和组织学评估遗漏了23%的结节微转移(MM)。我们的目标是通过集中分析最少数量的结节来标准化II期CC的病理和手术评估。我们推测，使用免疫组织化学(IHC)和多标记实时定量聚合酶链式反应(QRT)检测至少12个淋巴结(国家质量论坛最近认可的数字)将发现少于12个结节的标准苏木精-伊红(H&E)评估所遗漏的临床相关多发性骨髓瘤。与美国军事癌症研究所(USMCI)临床试验小组合作，最近报道了一项关于CC淋巴结分期的第三阶段随机试验，我们将在300名患者中进行一项重点分期的多中心前瞻性试验，这些患者的切除II期CC标本中至少有12个H&E染色阴性的淋巴结。由于患者不会接受辅助化疗，我们将能够确定IHC和/或QRT确定的结节性MM是否对无病生存率有影响。作为这项试验的必然结果，我们还将对原发肿瘤标本进行全面的转录分析；长期目标是基于原发肿瘤和淋巴结创建一个预后指数。这一指标应该有助于确定辅助治疗的候选对象。具体目的1.前瞻性地确定标本中含有=12 H&E阴性淋巴结的结节MM的IHC和/或分子(QRT)证据是否与II期CC切除后的无病生存相关。具体目的II.评价分子生物标记物在II期CC患者原发肿瘤中检测的预后意义。公共卫生相关性：使用高质量的手术、标准化的病理学和复杂的分子分析，这项试验将提供重要的信息，以确定哪些早期结肠癌患者可以单独通过手术治愈，哪些患者可能从化疗中受益。

DESCRIPTION (provided by applicant): The 20-30% rate of recurrence after surgical resection of stage II colon cancer (CC) suggests inadequate nodal sampling and/or inadequately sensitive and specific histologic assessment. Preliminary findings from our sentinel node (SN) study (CA 90484) demonstrate a 23% rate of nodal micrometastases (MM) missed by conventional sampling and histologic assessment. Our goal is to standardize the pathologic and surgical evaluation of stage II CC by focused analysis of a minimum number of nodes. We hypothesize that use of immunohistochemistry (IHC) and multimarker quantitative real-time PCR (qRT) assay to examine at least 12 LNs (a number recently endorsed by the National Quality Forum) will detect clinically relevant MM missed by standard hematoxylin and eosin (H&E) assessment of fewer than 12 nodes. In collaboration with the United States Military Cancer Institute (USMCI) Clinical Trials Group, which recently reported a Phase III randomized trial of nodal staging in CC, we will conduct a multicenter prospective trial of focused staging in 300 patients whose resected stage II CC specimens contain at least 12 nodes that stain negative with H&E. IHC will be performed and reviewed by USMCI pathologists, qRT assays and transcriptional analysis will be performed by UCLA scientists. Because patients will not receive adjuvant chemotherapy, we will be able to determine whether nodal MM identified by IHC and/or qRT have an impact on disease-free survival. As a corollary to this trial, we will also perform a comprehensive transcript analysis of the primary tumor specimens; the long-term goal is to create a prognostic index based on the primary tumor and LNs. This index should be helpful in identifying candidates for adjuvant therapy. Specific Aim I. To determine prospectively whether IHC and/or molecular (qRT) evidence of nodal MM in a specimen containing =12 H&E-negative LNs correlates with disease-free survival after resection of stage II CC. Specific Aim II. To evaluate the prognostic significance of molecular biomarkers detected in the primary tumor from patients with stage II CC. PUBLIC HEALTH RELEVANCE: Using quality surgery, standardized pathology and sophisticated molecular assays this trial will provide important information in determining which patients with early colon cancer are cured by surgery alone and which patients may benefit from chemotherapy.