Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ann Surg Oncol. 2013 Nov;20(12):4031-40. doi: 10.1245/s10434-012-2455-7. Epub 2012 Jun 26.
Microsatellite instability (MSI) and chromosomal instability are main mechanisms underlying colorectal carcinogenesis. We determined the features and prognosis of colorectal cancer based on MSI including mismatch repair genes and expression of p53.
Between 1999 and 2008, a total of 2,649 colorectal cancer patients were analyzed using a prospective database. A mismatch repair defect (MMR-D) was defined as a loss of expression of more than one MMR protein and/or MSI-high. MMR-proficiency (MMR-P) was defined as expression of all MMR proteins and microsatellite stable (MSS)/MSI-low. Groups 1 (G1), 2 (G2), 3 (G3), and 4 (G4) were defined as MMR-D and p53-positive expression, MMR-D and p53-negative expression, MMR-P and p53-positive expression, MMR-P and p53-negative expression, respectively.
Eighty-two (3.0%), 181 (6.8%), 1,368 (51.7%), and 1,018 (38.5%) patients were classified into groups 1-4, respectively. Comparison between G1 and G2 showed differences in location (p < 0.001), size (p = 0.030), node metastasis (p = 0.027), distant metastasis (p = 0.009), and stage (p = 0.040). Comparison between G3 and G4 showed differences in location (p < 0.001) and histology (p < 0.001). Comparison between G1 and G3 showed differences in location (p < 0.001) and histology (p < 0.001). Comparison between G2 and G4 showed differences in age (p < 0.001), location (p < 0.001), size (p = 0.006), histology (p < 0.001), node metastasis (p < 0.001), distant metastasis (p < 0.001), and stage (p < 0.001). On multivariate analysis, stage (p = 0.007) and histology (p < 0.001) were associated with improved overall survival, and stage (p < 0.001) was associated with disease-free survival.
According to the MSI and p53 subsets, colorectal cancers showed different clinicopathologic features, but these subsets had no prognostic impact on overall and disease-free survival rate.
微卫星不稳定性（MSI）和染色体不稳定性是结直肠癌发生的主要机制。我们根据包括错配修复基因和 p53 表达在内的 MSI 确定了结直肠癌的特征和预后。
1999 年至 2008 年间，我们使用前瞻性数据库分析了 2649 例结直肠癌患者。一个错配修复缺陷（MMR-D）被定义为一个以上的 MMR 蛋白表达缺失和/或 MSI-高。MMR-正常（MMR-P）被定义为所有 MMR 蛋白的表达和微卫星稳定（MSS）/MSI-低。第 1 组（G1）、第 2 组（G2）、第 3 组（G3）和第 4 组（G4）分别被定义为 MMR-D 和 p53 阳性表达、MMR-D 和 p53 阴性表达、MMR-P 和 p53 阳性表达、MMR-P 和 p53 阴性表达。
82 例（3.0%）、181 例（6.8%）、1368 例（51.7%）和 1018 例（38.5%）患者分别被归入 1-4 组。G1 与 G2 之间的比较在位置（p < 0.001）、大小（p = 0.030）、淋巴结转移（p = 0.027）、远处转移（p = 0.009）和分期（p = 0.040）上存在差异。G3 与 G4 之间的比较在位置（p < 0.001）和组织学（p < 0.001）上存在差异。G1 与 G3 之间的比较在位置（p < 0.001）和组织学（p < 0.001）上存在差异。G2 与 G4 之间的比较在年龄（p < 0.001）、位置（p < 0.001）、大小（p = 0.006）、组织学（p < 0.001）、淋巴结转移（p < 0.001）、远处转移（p < 0.001）和分期（p < 0.001）上存在差异。多因素分析显示，分期（p = 0.007）和组织学（p < 0.001）与总生存改善相关，分期（p < 0.001）与无病生存相关。
根据 MSI 和 p53 亚群，结直肠癌表现出不同的临床病理特征，但这些亚群对总生存率和无病生存率无预后影响。
