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足和/或敏感性和特异性组织学评估不足。我们的前哨淋巴结（SN）研究（CA 90484）的初步结果表明，传统采样和组织学评估漏诊的淋巴结微转移（MM）率为23%。我们的目标是通过对最少数量的淋巴结进行集中分析，使II期CC的病理和手术评估标准化。我们假设使用免疫组化（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量）将检测到标准苏木精和伊红（H&E）评估少于12个淋巴结时遗漏的临床相关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例患者中进行一项多中心前瞻性集中分期试验，这些患者切除的II期CC标本至少包含12个H&E染色阴性的淋巴结。将由USMCI病理学家进行和审查IHC，由UCLA科学家进行qRT测定和转录分析。由于患者将不接受辅助化疗，我们将能够确定通过IHC和/或qRT鉴定的淋巴结MM是否对无病生存期有影响。作为本试验的必然结果，我们还将对原发性肿瘤标本进行全面的转录本分析;长期目标是根据原发性肿瘤和淋巴结建立预后指数。这个指数应该有助于确定候选人的辅助治疗。具体目标一。前瞻性确定在含有≥ 12个H& E阴性LN的标本中淋巴结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。具体目标二。评估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：使用高质量的手术，标准化的病理学和复杂的分子检测，这项试验将提供重要的信息，以确定哪些早期结肠癌患者仅通过手术治愈，哪些患者可能受益于化疗。

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.