Tumor Markers and Recurrent Adenomas: A Follow-up Study

描述（申请人提供）：大多数结直肠癌是由腺瘤性息肉引起的，很大比例的腺瘤患者会发生复发性腺瘤。关于初次结肠镜检查后适当的监测间隔存在相当大的争议。评估复发性腺瘤的预测因素的研究将为设计个体化监测策略提供有价值的信息，特别是对于多发性腺瘤或病理进展的腺瘤患者。我们建议招募并跟踪2000名1996年至2001年间诊断为多发或晚期腺瘤的患者，以评估一组有希望的肿瘤标志物在预测腺瘤复发风险方面的效用。本研究提出的肿瘤标志物反映了腺瘤形成和发展过程中发生的主要事件。具体而言，我们将评估以下四组肿瘤标志物与腺瘤复发风险的关系：1)增殖和凋亡，包括凋亡指数（TUNEL测定）和Ki-67 （Mibl）、表皮生长因子受体（EGFR）和转化生长因子B受体II型（TGF-J3 RI）的表达；2)基因组不稳定性——染色体5q、l7p、15q、ip和18q上的杂合性缺失（LOH）事件；3)无翼/Writ信号通路- CTTNB1 （β -连环蛋白基因）、Cyclin D1、CMYC、COX2基因产物的表达；4) DNA甲基化- MLH1、MGMT、CDKN2A/P16和APC启动子的甲基化状态。研究患者将通过电话访谈和病历回顾相结合的方式进行随访。初始腺瘤的石蜡包埋块将被用于肿瘤标志物的生物测定。初始和复发性腺瘤的诊断将由研究病理学家审查和确认。本研究可能为确定高危腺瘤患者提供有价值的信息，以进行密切监测和化学预防。

DESCRIPTION (provided by applicant): Most colorectal cancers arise from adenomatous polyps, and a large proportion of patients with adenomas will develop recurrent adenomas. There is considerable controversy regarding the appropriate surveillance interval following initial colonoscopy. Studies assessing predictors for recurrent adenomas will provide valuable information for designing individualized surveillance strategies, particularly for patients with either multiple adenomas or pathologically advanced adenoma. We propose in this application to recruit and follow 2000 patients diagnosed in 1996 to 2001 with incident multiple or advanced adenomas to evaluate the utility of a panel of promising tumor markers in predicting the risk of adenoma recurrence. The tumor markers proposed for this study reflect major events that occur during the formation and progression of adenomas. Specifically, we will evaluate the following four groups of tumor markers in relation to the risk of adenoma recurrence: 1) proliferation and apoptosis, including the apoptosis index (TUNEL assay) and the expression of Ki-67 (Mibl), epidermal growth factor receptor (EGFR), and transforming growth factor B receptor type II (TGF-J3 RI]); 2) genomic instability - loss of heterozygosity (LOH) events on chromosomes 5q, l7p, 15q, ip, and 18q; 3) Wingless/Writ signaling pathway - expression of the CTTNB1 (Beta-catenin gene), Cyclin D1 CMYC, and COX2 gene products; and 4) DNA methylation - methylation status of the promoters of the MLH1, MGMT, CDKN2A/P16, and APC. Study patients will be followed through a combination of telephone interviews and medical chart reviews. Paraffin-embedded blocks of initial adenomas will be retrieved for bioassays of tumor markers. The diagnosis of initial and recurrent adenomas will be reviewed and confirmed by study pathologists. This study is likely to provide valuable information for identifying high-risk adenoma patients for close surveillance and chemoprevention.