Tumor Markers and Recurrent Adenomas: A Follow-up Study

描述（由申请人提供）：大多数结直肠癌起源于腺瘤性息肉，并且大部分腺瘤患者将发展为复发性腺瘤。关于首次结肠镜检查后的适当监测间隔存在相当大的争议。评估复发性腺瘤预测因子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性腺瘤的患者。在本申请中，我们建议招募并随访2000例在1996年至2001年诊断为多发性或晚期腺瘤的患者，以评估一组有希望的肿瘤标记物在预测腺瘤复发风险中的效用。本研究提出的肿瘤标志物反映了腺瘤形成和进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法）和Ki-67（Mibl）、表皮生长因子受体（EGFR）和转化生长因子B受体II型的表达（TGF-J3 RI]）; 2）基因组不稳定性-染色体5 q、17 p、15 q、ip和18 q上的杂合性丢失（洛）事件; 3）Wingless/Writ信号传导途径-CTTNB 1的表达（β-连环蛋白基因）、细胞周期蛋白D1 CMYC和COX 2基因产物;和4）MLH 1、MGMT、CDKN 2A/P16和APC的启动子的DNA甲基化-甲基化状态。将通过电话访谈和病历审查相结合的方式对研究患者进行随访。将取出初始腺瘤的石蜡包埋块，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。这项研究可能提供有价值的信息，以确定高风险腺瘤患者的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.