原发性肝癌p53基因高频缺失的双色荧光原位杂交证据

Evidence for high-frequent deletion of p53 gene in primary hepatocellular carcinoma by interphase dual fluorescence in situ hybridization

目的 :探讨原发性肝癌 (HCC)中p5 3基因的缺失频率、方式、特点及其临床意义。方法 :以p5 3基因及 17号染色体着丝粒DNA为探针 ,应用间期双色荧光原位杂交 (interphasedual,FISH)技术。结果 :肝癌中p5 3基因的缺失频率为 68 0 % (68/ 10 0 ) ,而配对正常肝组织中则未见有p5 3缺失 ;p5 3缺失方式多样且往往伴随 17号染色体多倍体 (r=0 5 94,P <0 0 1) ;p5 3缺失与肝癌病人的性别、年龄、HBV感染及临床分期无显著相关 (P >0 0 5 ) ,但与血清甲胎蛋白 (AFP)水平、肿瘤大小则显著相关 (P <0 0 5 ) ;有无p5 3缺失病人之间 2年存活率差异非常显著 (χ2 =11 463 ,P <0 0 1)。结论 :p5 3基因在原发性肝癌中存在高频缺失并往往伴随 17号染色体的多倍体 ;双色FISH技术为评估基因的缺失提供了特异、敏感、直观的分子细胞遗传学证据。

AIM: To investigate the frequency and pattern of deletion of p53 gene in primary hepatocellular carcinoma (HCC) and its clinical significance. METHODS: The interphase dual fluorescence in situ hybridization(FISH) technique was applied to detect loss of p53 gene in HCCs. RESULTS: The deletion of p53 gene was found in 68.0% of HCCs whereas no loss of p53 gene was detected in 40 mated normal liver specimens. Loss of p53 gene was closely related to tumor size and serum α-fetoprotein(AFP) level in HCC patients ( P< 0.05) but not to HCC patients' sex, age, HBV infection and clinical staging ( P> 0.05). The 2-year survival rate of postoperative HCC patients was significantly lower in the HCC cases with p53 gene deletion (25.6%) than those without p53 gene loss (69.6%) ( χ 2=11.463, P< 0.01). CONCLUSIONS: There is a high frequency of the deletion of p53 gene in primary HCCs. Dual FISH technique provides specific, sensitive and direct evidence for molecular cytogenetic evaluation of gene deletion in tumors.