Microsatellite Instability and Loss of Heterozygosity at Chromosomal Location 18q: Prospective Evaluation of Biomarkers for Stages II and III Colon Cancer-A Study of CALGB 9581 and 89803
Microsatellite Instability and Loss of Heterozygosity at Chromosomal Location 18q: Prospective Evaluation of Biomarkers for Stages II and III Colon Cancer-A Study of CALGB 9581 and 89803
复制标题
DOI：
10.1200/jco.2010.33.0092
复制
发表时间：
2011-08-10
影响因子：
45.3
通讯作者：
Warren, Robert S.
中科院分区：
文献类型：
--
作者：
Bertagnolli, Monica M.;Redston, Mark;Warren, Robert S.
结直肠癌（colorectal cancer，CRC）是一系列基因组变化累积的结果，这些变化导致癌基因激活和抑癌基因丢失。这些特点可能会分类CRC到子集的不同clinical behaviors.Patients和MethodsWe研究了两个这些基因组缺陷-错配修复缺陷（MMR-D）和杂合性丢失在染色体位置18 q（18 qLOH）-在患者参加到两个III期合作组试验治疗潜在的可治愈的结肠癌。这些试验包括前瞻性二次分析，以确定这些标志物和治疗结果之间的关系。共检测1,852例患者的MMR状态和955例患者（排除MMR-D肿瘤患者）的18 qLOH。结果与III期相比，更多的II期肿瘤为MMR-D（21.3%v14.4%，P <0.001）和18 q完整（24.2%v15.1%，P = 0.001）。对于联合队列，MMR-D肿瘤患者的5年无病生存率（DFS; 0.76 v0.67; P <0.001）和总生存率（OS; 0.81 v0.78; P = 0.029）优于MMR完整（MMR-I）肿瘤患者。在MMR-I肿瘤患者中，18 q的状态不影响预后，18 q完整与18 qLOH肿瘤患者的5年值分别为0.74与0.65（P = .18）DFS和0.81与0.77（P = 0.18）的OS.ConclusionWe的结论是，MMR-D肿瘤状态，但不存在18 qLOH，具有预后价值的II期和III期结肠癌。
PurposeColorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors.Patients and MethodsWe studied two of these genomic defects-mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH)-in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH.ResultsCompared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS.ConclusionWe conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.