Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
J Clin Oncol. 2011 Aug 10;29(23):3153-62. doi: 10.1200/JCO.2010.33.0092. Epub 2011 Jul 11.
Colorectal 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.
We 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.
Compared 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.
We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.
结直肠癌（CRC）是一系列累积的基因组变化的结果，这些变化产生了致癌基因的激活和肿瘤抑制基因的丢失。这些特征可能将 CRC 分为具有不同临床行为的亚组。
我们研究了两种基因组缺陷——错配修复缺陷（MMR-D）和染色体 18q 位置杂合性丢失（18qLOH）——在参加两个有希望治愈的结肠癌的 III 期合作组试验的患者中。这些试验包括前瞻性的二次分析，以确定这些标志物与治疗结果之间的关系。共有 1852 名患者接受了 MMR 状态检测，955 名患者（不包括 MMR-D 肿瘤患者）接受了 18qLOH 检测。
与 III 期相比，更多的 II 期肿瘤是 MMR-D（21.3%比 14.4%；P<0.001），并且在 18q 上是完整的（24.2%比 15.1%；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 比 0.67；P<0.001）和总生存率（OS；0.81 比 0.78；P=0.029）优于 MMR 完整（MMR-I）肿瘤患者。在 MMR-I 肿瘤患者中，18q 的状态并不影响预后，18q 完整与 18qLOH 肿瘤患者的 5 年 DFS 值分别为 0.74 比 0.65（P=0.18），OS 值分别为 0.81 比 0.77（P=0.18）。
我们得出结论，MMR-D 肿瘤状态，但不是 18qLOH 的存在，对 II 期和 III 期结肠癌具有预后价值。
