Prognostic relevance of 20q13 gains in sporadic colorectal cancers:: a FISH analysis
Prognostic relevance of 20q13 gains in sporadic colorectal cancers:: a FISH analysis
复制标题
DOI：
10.1080/00365520410003191
复制
发表时间：
2004-08-01
影响因子：
1.9
通讯作者：
Baretton, GB
中科院分区：
文献类型：
--
作者：
Aust, DE;Muders, M;Baretton, GB
背景资料：20 q13的扩增是实体瘤中常见的染色体改变，并含有许多推定的癌基因（CAS/CSE 1-L、NABC 1或Aurora 2）。20 q13上的扩增已被确定为一个独立的预后标志物，表明乳腺癌和卵巢癌的生存率较差。然而，关于20 q13增加在散发性结直肠癌中的潜在意义知之甚少。本研究的目的是将散发性结直肠癌中20 q13的增加与其他已知的预后因素、肿瘤进展和总生存率相关联。研究方法：从146例不同UICC分期的石蜡包埋结直肠癌中提取细胞核，并使用20q13.2（VYSIS）直接标记探针进行荧光原位杂交（FISH）。每个样品在120个细胞核中计数信号。当>40%的细胞核显示3个或更多FISH信号时，认为20 q13获得。用对数秩检验和Kaplan-Meier生存曲线检验统计学相关性。结果：78例（53%）获得20q13.2信号。在单变量和多变量分析中，20q13.2增加的病例比没有增加的病例的结局更差：20q13.2增加是总生存率（P = 0.006）和肿瘤转移（P = 0.012）的独立预后指标。20q13.2的增加与肿瘤分期无关。然而，20q13.2增益和肿瘤在左半结肠的位置之间存在显著相关性，组织学分级和20q13.2增益之间呈负相关。结论：这些数据表明，20q13.2的增加与肿瘤进展更快和患者生存率更差相关，与肿瘤大小和淋巴结受累无关。因此，20 q13的改变是结直肠肿瘤进展中具有独立预后相关性的重要生物学事件。
Background: Amplification of 20q13 is a frequent chromosomal alteration in solid tumors and harbors a number of putative oncogenes (CAS/CSE1-L, NABC1, or Aurora2). Amplifications on 20q13 have been identified as an independent prognostic marker indicating worse survival in breast and ovarian cancer. However, little is known about the propostic significance of 20q13 gains in sporadic colorectal cancers. The aim of this study was to correlate 20q13 gains in sporadic colorectal cancers with other known prognostic factors, tumor progression, and overall survival. Methods: Nuclei were extracted from 146 paraffin-embedded colorectal cancers of different UICC stages and used for fluorescence in situ hybridization (FISH) with a directly labeled probe for 20q13.2 (VYSIS). Signals were counted in 120 nuclei per sample. 20q13 was considered gained when >40% of the nuclei showed 3 or more FISH signals. Statistical correlations were tested with log-rank tests and Kaplan-Meier survival curves. Results: Signal numbers for 20q13.2 were gained in 78 cases (53%). Cases with gains on 20q13.2 showed worse outcome than cases without: the gain of 20q13.2 was an independent prognostic market for overall survival (P = 0.006) as well as tumor progession (P = 0.012) in univariate and multivariate analyses. Gains on 20q13.2 did not correlate with tumor stage. However, there was a significant association between 20q13.2 gains and tumor location in the left-sided colon and an inverse correlation between histologic grade and 20q13.2 gains. Conclusion: These data indicate that gains on 20q13.2 correlate with faster tumor progression and worse patient survival independent from tumor size and lymph node involvement. Therefore, alterations on 20q13 are an important biological event in colorectal tumor progression with independent prognostic relevance.