Tumor Markers and Recurrent Adenomas: A Follow-up Study

描述(申请人提供)：大多数结直肠癌起源于腺瘤性息肉，并且很大比例的腺瘤患者会发展为复发性腺瘤。对于初次结肠镜检查后的适当监测间隔，有相当大的争议。评估腺瘤复发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期腺瘤患者。在这项应用中，我们建议招募并跟踪1996-2001年间诊断为多发性或晚期腺瘤的2000名患者，以评估一组有前途的肿瘤标志物在预测腺瘤复发风险方面的作用。这项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。具体地说，我们将评估以下四组肿瘤标志物与腺瘤复发的风险：1)增殖和凋亡，包括凋亡指数(TUNEL法)和Ki-67(Mib1)、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-染色体5q、17p、15q、IP和18q上的杂合性缺失(LOH)事件；3)Wingless/WRIT信号通路-CTTNB1(Beta-catenin基因)、Cyclin D1cMYC和COX2基因产物的表达；4)MLH1、MGMT、CDKN2A/P16和APC启动子的DNA甲基化状态。研究患者将通过电话采访和病历审查相结合的方式进行跟踪调查。石蜡包埋的初始腺瘤块将被取出用于肿瘤标志物的生物分析。初发腺瘤和复发性腺瘤的诊断将由研究病理学家进行复习和确认。这项研究可能会为识别高危腺瘤患者进行密切监测和化学预防提供有价值的信息。

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.