肝细胞癌细胞凋亡、增殖及其相关调控因子表达的研究

Study on the expression of apoptosis, proliferation and the related regulation factors in hepatocellular carcinoma

目的 探讨肝细胞癌中细胞凋亡、增殖及其相关调控因子表达特征与HCC分化状态的关系。方法 分别以末端脱氧核苷酸转移酶 (TdT)介导的d UTP缺口末端标记技术 (TUNEL)和SP免疫组化方法检测 3 5例人HCC与其癌旁组织中凋亡细胞和增殖细胞核抗原 (PCNA)及p5 3、Fas的表达特征 ,并结合临床资料进行分析。结果 凋亡细胞在HCC组织中呈散在分布 ,其凋亡细胞指数显著低于癌旁组织 ,而PCNA指数明显高于癌旁组织 ;在HCCⅠ、Ⅱ、Ⅲ、Ⅳ级中 ,凋亡细胞指数分别为 0 5 3 ,0 42 ,0 2 0 ,0 2 1。PCNA指数分别为 0 0 6,0 41,0 63 ,0 80 ,均存在显著性差异 ;HCC组织的p5 3表达随Edmondson分级呈递增现象 ;而Fas均呈低水平表达。结论 HCC的分化程度与细胞凋亡指数呈正相关 ,而与PCNA指数呈负相关。HCC细胞凋亡为p5 3依赖型 ,p5 3基因高突变、Fas表达的下调的肝癌组织其恶性程度较高 。

Objective To investigate the expression of apoptosis, proliferation and the related regulation factors in hepatocellular carcinoma (HCC). Methods Apoptosis, nuclear antigen of proliferating cells (PCNA), p53 and Fas protein were detected by labeling technique of in situ terminal deoxynucleotide transferase and immunohistochemical method in 35 HCC and tumor adjacent specimens. Results The index of apoptotic cells scattered in HCC tissue was significantly lower than that in adjacent tissue. However, the index of PCNA was much higher in HCC than that in adjacent tissue. Importantly, the apoptotic index of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of HCC was 0.53, 0.42, 0.20, 0.21 and the index of PCNA was 0.06 , 0.41 , 0.63, 0.80, respectively. There was a marked statistical difference ( P <0.01) both in the index of PCNA and apoptosis among the various stages. The p53 expression in HCC increased with Edmondson stages. However, the Fas expression was at low level. Conclusion Tumor differentiation is positively correlated to the apoptotic index but negatively to the index of PCNA in HCC. The apoptosis in HCC occurs in a p53 dependent manner. The higher mutant of p53 and the lower regulation of Fas expression may contribute to the genesis and progression of HCC.