基因和表观遗传分类定义了临床表型，并决定了结直肠癌患者的预后。

Genetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer.

作者信息

Sanchez J A, Krumroy L, Plummer S, Aung P, Merkulova A, Skacel M, DeJulius K L, Manilich E, Church J M, Casey G, Kalady M F

机构信息

Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio, USA.

出版信息

Br J Surg. 2009 Oct;96(10):1196-204. doi: 10.1002/bjs.6683.

DOI:10.1002/bjs.6683

PMID:19787768

Abstract

BACKGROUND

A molecular classification of colorectal cancer has been proposed based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in the KRAS and BRAF oncogenes. This study examined the prevalence of these molecular classes, and differences in clinical presentation and outcome.

METHODS

Demographics, tumour characteristics and survival were recorded for 391 subjects with colorectal cancer. Tumour DNA was analysed for MSI (high (MSI-H) or microsatellite stable (MSS)), CIMP (high (CIMP-H) or no (CIMP-neg)) and BRAF and KRAS mutations. Clinical differences between four phenotypes were examined.

RESULTS

Most tumours were MSS/CIMP-neg (69.8 per cent), with a nearly equal distribution of MSI-H/CIMP-H, MSI-H/CIMP-neg and MSS/CIMP-H types. MSS/CIMP-neg tumours were less likely to be poorly differentiated (P = 0.009). CIMP-H tumours were more common in older patients (P < 0.001). MSI-H/CIMP-H tumours had a high frequency of BRAF mutation and a low rate of KRAS mutation; the opposite was true for MSS/CIMP-neg tumours (P < 0.001). The four molecular phenotypes tended towards divergent survival (P = 0.067 for stages 1-III). MSI-H cancers were associated with better disease-free survival (hazard ratio 2.00 (95 per cent confidence interval 1.03 to 3.91); P = 0.040).

CONCLUSION

Colorectal cancers are molecularly and clinically heterogeneous. These different molecular phenotypes may reflect variable prognosis.

摘要

背景

基于微卫星不稳定性（MSI）、CpG岛甲基化表型（CIMP）以及KRAS和BRAF癌基因的突变，有人提出了结直肠癌的分子分类。本研究调查了这些分子类别在结直肠癌中的流行情况，以及临床表现和预后的差异。

方法

记录了391例结直肠癌患者的人口统计学信息、肿瘤特征和生存情况。对肿瘤DNA进行分析，检测MSI（高（MSI-H）或微卫星稳定（MSS））、CIMP（高（CIMP-H）或无（CIMP-neg））以及BRAF和KRAS突变情况。研究了四种表型之间的临床差异。

结果

大多数肿瘤为MSS/CIMP-neg（69.8%），MSI-H/CIMP-H、MSI-H/CIMP-neg和MSS/CIMP-H类型的分布几乎相等。MSS/CIMP-neg肿瘤分化差的可能性较小（P = 0.009）。CIMP-H肿瘤在老年患者中更为常见（P < 0.001）。MSI-H/CIMP-H肿瘤BRAF突变频率高，KRAS突变率低；MSS/CIMP-neg肿瘤则相反（P < 0.001）。四种分子表型在生存方面有分化趋势（I-III期患者中P = 0.067）。MSI-H癌症与较好的无病生存率相关（风险比2.00（95%置信区间1.03至3.91）；P = 0.040）。