摘要
目的 检测原发性肝细胞癌中 17号染色体上p5 3基因的缺失与HER 2基因的扩增并探讨其临床意义。方法 分别以不同颜色荧光标记的p5 3基因、HER 2基因和 17号染色体着丝粒为双色探针组 ,应用间期双色荧光原位杂交 (FISH)技术检测 42例肝细胞癌间期细胞核中p5 3基因、HER 2基因和 17号染色体的拷贝数及其相对比例 ,以确定其缺失或扩增 ,结合临床分期、血清甲胎蛋白 (AFP)、肿瘤大小等资料进行统计分析其临床意义。结果 42例肝细胞癌中p5 3基因缺失 2 7例( 64 3 % ) ;HER 2基因扩增 9例 ( 2 1 4% ) ,其中高拷贝扩增 (HC) 4例 ( 9 5 % ) ,低拷贝扩增 (LC) 5例( 11 9% ) ,同时具有缺失与扩增的 6例 ( 14 3 % ) ;另外 ,17号染色体多倍体有 2 6例 ( 61 9% )。p5 3基因缺失与 17号染色体多倍性呈正相关 ( χ2 =12 2 86,P <0 0 0 1) ,但与HER 2基因的扩增无关 ( χ2 =0 0 0 ,P =1 0 0 )。p5 3基因缺失与肝细胞癌患者AFP水平、肿瘤大小有关 (P <0 0 5 ) ;术后 2年存活率p5 3基因缺失患者 ( 18 5 % )显著低于无缺失患者 ( 60 0 % ,χ2 =7 467,P =0 0 0 6)。结论 原发性肝细胞癌的17号染色体上存在p5 3基因高频缺失和HER 2基因的扩增 。
Objective To investigate the deletion of p53 gene and amplification of HER-2 oncogene at chromosome 17 in primary hepatocellular carcinoma (HCC) and the clinical significance. Methods Interphase dual fluorescence in situ hybridization (FISH) was applied to detect the ratio of the number of p53 gene copy or HER-2 oncogene copy to that of chromosome 17 copy, to determine the p53 gene deletion and HER-2 oncogene amplification in nuclei prepared from 42 surgical specimens of HCC. Statistical analysis for their clinical significance was performed. Results Loss of p53 gene and amplification of HER-2 oncogene were detected in 27 (64.3%) and 9 (21.4%) of the 42 HCC respectively including 4 cases with low and 5 with high copy amplification. Six (14.3%) of 42 HCC showed simultaneously p53 gene deletion and HER-2 oncogene amplification. 61.9% (26/42) of HCC were polysomy 17, which correlated positively with p53 gene deletion (χ 2=12.286,P<0.001). No close correlation between p53 gene loss and HER-2 oncogene amplification was found (χ 2=0.00,P=1.00 ). Loss of p53 gene was related to the serum alpha-fetoprotein (AFP) level and the tumor size (P<0.05). The postoperative 2-year survival rate (18.5%) of HCC patients with p53 gene deletion was significantly lower than postoperative 2-year survival rate (60.0%) of those without p53 gene loss (χ 2=7.467,P=0.006). Meanwhile, HER-2 oncogene amplification showed a tendency of correlation with the tumor size (χ 2=2.973,P=0.085), and the postoperative 2-year survival rate (0/9) of HCC patients with HER-2 oncogene amplification was significantly lower than those (42.4%) without HER-2 oncogene amplification (χ 2=3.977,P=0.046). Conclusion There were a high frequency of p53 gene deletion and a low frequency of HER-2 oncogene amplification in primary HCC, which might be involved in initiation and development of a subset of primary HCC.
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2003年第1期20-24,共5页
Chinese Journal of Pathology
基金
国家杰出青年B类基金资助项目 ( 3982 5 5 11)
广东省自然科学基金资助项目 ( 980 10 7)
关键词
肝细胞癌
P53基因
基因缺失
HER-2基因
基因扩增
临床分期
甲胎蛋白
Carcinomas, hepatocellular
Liver neoplasms
Genes,p53
Genes, erbB-2
Gene deletion
Gene amplification
Chromosomes,human,pair 17
In situ hybridization,fluorescence
