Low microsatellite instability is associated with poor prognosis in stage C colon cancer

被引:95
作者
Kohonen-Corish, MRJ
Daniel, JJ
Chan, C
Lin, BPC
Kwun, SY
Dent, OF
Dhillon, VS
Trent, RJA
Chapuis, PH
Bokey, EL
机构
[1] Univ New S Wales, Canc Res Program, Garvan Inst Med Res, St Vincents Hosp, Darlinghurst, NSW 2010, Australia
[2] Univ Sydney, Discipline Med, Sydney, NSW 2006, Australia
[3] Univ Sydney, Discipline Pathol, Sydney, NSW 2006, Australia
[4] Royal Prince Alfred Hosp, Dept Mol & Clin Genet, Sydney, NSW, Australia
[5] Concord Hosp, Dept Pathol Anat, Sydney, NSW, Australia
[6] Concord Hosp, Dept Colorectal Surg, Sydney, NSW, Australia
[7] Univ Sydney, Sydney, NSW 2006, Australia
关键词
D O I
10.1200/JCO.2005.00.109
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose The significance of low microsatellite instability (MSI-L) in colorectal cancer is poorly understood. No clear biologic distinction has been found between MSI-L and microsatellite stable (MSS) colorectal cancer, and these two phenotypes are usually combined when analyzed against the well-defined high MSI (MSI-H) phenotype. Evidence is emerging that an O-6-methylguanine DNA methyltransferase (MGMT) gene defect is associated with MSI-L. Therefore, to further define this phenotype, we undertook a detailed analysis of the prognostic significance of MSI-L and loss of MGMT expression in colon cancer. Patients and Methods The study cohort was 183 patients with clinicopathologic stage C colon cancer who had not received adjuvant therapy. We analyzed MSI status, MGMT and mismatch repair protein expression, as well as MGMT and p 16 promoter hype rm ethylation. Results We showed that MSI-L defines a group of patients with poorer survival (P =.026) than MSS patients, and that MSI-L was an independent prognostic indicator (P =.005) in stage C colon cancer. Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival. Conclusion MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.
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页码:2318 / 2324
页数:7
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