[微卫星和染色体稳定型结直肠癌患者染色体异常的意义及特征]

[The significance and characteristics of chromosomal abnormalities in patients with microsatellite and chromosome stable colorectal carcinoma].

作者信息

Xie Dan, Wu Hui-Xi, Liu Yong-Dong, Zeng Sui-de, Lin Feng

机构信息

State Key Laboratory of Oncology in Southern China, Caner Center, Sun Yat-Sen University, Guangzhou, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Jan 2;87(1):11-5.

PMID:17403304

Abstract

OBJECTIVE

To investigate the clinico-pathological significance and characteristics of chromosomal abnormalities in microsatellite and chromosome stable (AMCS) colorectal carcinoma (CRC).

METHODS

Flow cytometry, microsatellite instability analysis and immunohistochemistry methods were used to examine the DNA ploidy, microsatellite instability and expression of mismatch repair proteins (hMSH(2) and hMSH(1)) in 156 cases of CRCs, so as to select the MACS CRCs. Comparative genomic hybridization (CGH) method was subsequently performed to analyze the status of chromosomal abnormalities of MACS CRCs. The correlation between chromosomal changes of MACS CRC and patients clinico-pathological features was further evaluated.

RESULTS

Of the 156 CRCs studied, fourty-one (26%) cases were observed both diploid/near diploid DNA content and stable microsatellite sequence and all these CRCs showed normal expression of hMSH(2) and hMSH(1) protein, and thus, defined as MACS CRC. Our CGH results showed that the overall mean numbers of chromosomal abnormality of 41 MACS CRCs was 9.6. The chromosomal arms with DNA amplification (frequency > or = 10%) were 20 q (68%), 13 q (56%), 7 q (49%), 13 p (39%), 20 p (37%), 8 q (30%), 1 q (22%), 11 q (15%), 16 q (12%) and 2 p, 4 q, 10 q (10%). The chromosomal arms with DNA deletion (frequency > or = 10%) were 18 q (63%), 8 p (51%), 17 p (37%), 1 p (30%), 3 p (26%), 4 p, 13 q, 14 (15%) and 21 q, Xp (10%). In addition, there was 79% and 82% MACS CRCs in Dukes'C/D stages observed amplification of 20 q and deletion of 18 q, respectively, the frequency was significantly higher that that in Dukes'A/B stages (46%, P = 0.038 and 21%, P = 0.0009).

CONCLUSIONS

The overall number of chromosomal abnormalities in MACS CRCs is similar to that of chromosomal instable (CI) CRCs, but is higher than that of microsatellite instable (MSI) CRCs. The frequent deletion of 8 p in MACS CRCs might be a special molecular event that is different from CRCs in CI and MSI pathway. Both 20 q amplification and 18 q deletion are the most frequent chromosomal abnormalities in MACS CRC and are associated closely with tumor's malignant clinical phenotype. These chromosomal changes might play important roles the development and progression of MACS CRC.

摘要

目的

探讨微卫星和染色体稳定（AMCS）型结直肠癌（CRC）中染色体异常的临床病理意义及特征。

方法

采用流式细胞术、微卫星不稳定性分析及免疫组化方法检测156例CRC的DNA倍体、微卫星不稳定性及错配修复蛋白（hMSH(2)和hMSH(1)）表达，筛选出MACS CRC。随后采用比较基因组杂交（CGH）方法分析MACS CRC的染色体异常情况。进一步评估MACS CRC染色体变化与患者临床病理特征的相关性。

结果

在研究的156例CRC中，41例（26%）观察到二倍体/近二倍体DNA含量及稳定的微卫星序列，且所有这些CRC均显示hMSH(2)和hMSH(1)蛋白表达正常，因此被定义为MACS CRC。我们的CGH结果显示，41例MACS CRC的染色体异常总数平均为9.6。DNA扩增（频率≥10%）的染色体臂为20q（68%）、13q（56%）、7q（49%）、13p（39%）、20p（37%）、8q（30%）、1q（22%）、11q（15%）、16q（12%）以及2p、4q、10q（10%）。DNA缺失（频率≥10%）的染色体臂为18q（63%）、8p（51%）、17p（37%）、1p（30%）、3p（26%）、4p、13q、14（15%）以及21q、Xp（10%）。此外，在Dukes'C/D期的MACS CRC中，分别有79%和82%观察到20q扩增和18q缺失，其频率显著高于Dukes'A/B期（46%，P = 0.038和21%，P = 0.0009）。

结论

MACS CRC的染色体异常总数与染色体不稳定（CI）型CRC相似，但高于微卫星不稳定（MSI）型CRC。MACS CRC中8p的频繁缺失可能是一种特殊的分子事件，不同于CI和MSI途径的CRC。20q扩增和18q缺失均是MACS CRC中最常见的染色体异常，且与肿瘤的恶性临床表型密切相关。这些染色体变化可能在MACS CRC的发生发展中起重要作用。