Ultrastaging of Early Colon Cancer

描述（由申请人提供）：II期结肠癌（CC）手术切除后20-30%的复发率表明淋巴结取样不充分和/或敏感性和特异性组织学评估不充分。我们的前哨淋巴结（SN）研究（CA 90484）的初步结果显示，23%的淋巴结微转移（MM）被常规抽样和组织学评估遗漏。我们的目标是通过集中分析最小数量的淋巴结来标准化II期CC的病理和手术评估。我们假设使用免疫组织化学（IHC）和多标记定量实时PCR （qRT）检测至少12个淋巴结（最近由国家质量论坛认可的数字）将检测出少于12个淋巴结的标准苏木精和伊红（H&E）评估遗漏的临床相关MM。与美国军事癌症研究所（USMCI）临床试验组合作，最近报告了一项CC淋巴结分期的III期随机试验，我们将在300名切除的II期CC标本中包含至少12个H&E染色阴性的淋巴结的患者中进行一项多中心前瞻性集中分期试验。IHC将由USMCI病理学家进行和审查，qRT分析和转录分析将由加州大学洛杉矶分校的科学家进行。由于患者不会接受辅助化疗，我们将能够确定通过免疫组化和/或qRT识别的淋巴结性MM是否对无病生存有影响。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；长期目标是建立一个基于原发肿瘤和LNs的预后指标。该指标应有助于确定辅助治疗的候选人。前瞻性地确定在含有=12个h&e阴性LNs的标本中淋巴结性MM的免疫组化和/或分子（qRT）证据是否与II期CC切除后的无病生存相关。为了评估在II期CC患者原发肿瘤中检测到的分子生物标志物的预后意义。公共卫生相关性：通过高质量的手术、标准化的病理学和复杂的分子分析，本试验将为确定哪些早期结肠癌患者仅通过手术治愈，哪些患者可能从化疗中受益提供重要信息。

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.