微卫星不稳定性作为结肠癌和直肠癌预后和肿瘤反应标志物的差异影响。
The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer.
机构信息
Division of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
出版信息
Eur J Cancer. 2012 May;48(8):1235-43. doi: 10.1016/j.ejca.2011.10.005. Epub 2011 Nov 7.
BACKGROUND
Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response.
METHODS
PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer.
RESULTS
Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU-based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104).
CONCLUSION
These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours.
背景
微卫星不稳定性（MSI）是结直肠癌的一种独特分子表型，与预后和对 5-氟尿嘧啶（5-FU）为基础的化疗的肿瘤反应有关。我们研究了 MSI 在结肠癌和直肠癌之间的差异影响，作为预后和化疗反应的标志物。
方法
对 1125 名患者进行了基于 PCR 的 MSI 检测。660 名患者（58.7%）患有结肠癌，465 名患者（41.3%）患有直肠癌。
结果
在 1125 名患者中，有 106 名（9.4%）患有高频 MSI（MSI-H）肿瘤。MSI-H 结肠癌（13%）具有独特的表型，包括诊断时年龄较轻、结直肠癌家族史、早期肿瘤、淋巴结、转移（TNM）分期、近端位置、分化不良和高水平的基线癌胚抗原（CEA），而 MSI-H 直肠癌（4.3%）除了结直肠癌家族史外，与 MSS/MSI-L 肿瘤具有相似的临床病理特征。与 MSS/MSI-L 肿瘤相比，MSI-H 肿瘤与更长的无病生存（DFS）（P=0.005）和总生存（OS）（P=0.009）相关，而在直肠癌中没有观察到这些正相关。接受 5-FU 为基础的化疗的 MSS/MSI-L 肿瘤患者预后良好（P=0.013），但在 MSI-H 中没有观察到这种正相关（P=0.104）。
结论
这些结果支持将 MSI 状态作为结肠癌患者预后和 5-FU 为基础的化疗反应的标志物。需要进一步研究以评估 MSI 在直肠癌患者中的精确作用以及 MSI-H 肿瘤中 5-FU 为基础的化疗的效果。
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