基于染色体缺失和微卫星不稳定性的结直肠癌基因分类可预测生存率。

Genetic classification of colorectal cancer based on chromosomal loss and microsatellite instability predicts survival.

作者信息

Choi Sang-Wook, Lee Kyung Jun, Bae Young-An, Min Ki-Ouk, Kwon Mi-Seon, Kim Kyoung-Mee, Rhyu Mun-Gan

机构信息

Departments of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.

出版信息

Clin Cancer Res. 2002 Jul;8(7):2311-22.

PMID:12114436

Abstract

PURPOSE

Colorectal cancers harbor one of two distinct alterations, unilateral chromosomal loss as evidenced by a loss of heterozygosity (LOH) and microsatellite instability (MSI), as represented by the widespread insertion or deletion of simple repeat nucleotides. We investigated the relationships between the clinicopathological features and microsatellite alterations (LOH and MSI) of 168 colorectal cancers.

EXPERIMENTAL DESIGN

The concerted and individual effects of various chromosomal losses on survival were comparatively analyzed using a reference panel of 40 microsatellite markers in eight cancer-related chromosomes, 3p, 4p, 5q, 8p, 9p, 13q, 17p, and 18q.

RESULTS

Of the 168 colorectal cancers tested, 29 (17%) with high-frequency MSI were associated with good survival (P < 0.05). The extent of LOH detected in 139 (83%) cases without MSI was classified as low level involving three or fewer arms (35%), moderate level involving four arms (22%), or high level involving five or more arms (43%). High-level loss correlated with earlier onset, lymphatic invasion, and rectal location, whereas low-level loss was more common in proximal colon and stages I and II (P < 0.05). The survival curve and multivariate analysis identified high- and low-level chromosomal loss as the most significant predictor of poor and good survival, respectively (log-rank test, P < 0.0001), in patients with stage II (hazard ratio, 6.27; 95% confidence interval, 1.99-19.7; P = 0.0017) and those with stage III (hazard ratio, 10.89; 95% confidence interval, 2.54-46.77; P = 0.0013). Moderate chromosomal loss showed dual prognostic values associated with favorable stage II and unfavorable stage III. Single chromosomal losses tended to play a role as a part of the concerted chromosomal function.

CONCLUSION

The classification of colorectal cancer based on chromosomal loss and MSI provides a prognostic index that reflects tumor pathobiology.

摘要

目的

结直肠癌存在两种不同的改变，一种是杂合性缺失（LOH）所证实的单侧染色体缺失，另一种是微卫星不稳定性（MSI），表现为简单重复核苷酸的广泛插入或缺失。我们研究了168例结直肠癌的临床病理特征与微卫星改变（LOH和MSI）之间的关系。

实验设计

使用包含40个微卫星标记的参考面板，对8条癌症相关染色体（3p、4p、5q、8p、9p、13q、17p和18q）上各种染色体缺失对生存的协同和个体影响进行了比较分析。

结果

在检测的168例结直肠癌中，29例（17%）高频MSI与良好的生存率相关（P < 0.05）。在139例（83%）无MSI的病例中检测到的LOH程度分为低水平（涉及三个或更少臂，35%）、中等水平（涉及四个臂，22%）或高水平（涉及五个或更多臂，43%）。高水平缺失与发病较早、淋巴浸润和直肠部位相关，而低水平缺失在近端结肠以及I期和II期更为常见（P < 0.05）。生存曲线和多变量分析确定，高水平和低水平染色体缺失分别是II期（风险比，6.27；95%置信区间，1.99 - 19.7；P = 0.0017）和III期（风险比，10.89；95%置信区间，2.54 - 46.77；P = 0.0013）患者生存不良和良好的最显著预测因素。中等染色体缺失显示出与II期良好和III期不良相关的双重预后价值。单个染色体缺失倾向于作为协同染色体功能的一部分发挥作用。