小肝癌中端粒酶蛋白hTRT基因检测与P53、N-ras、nm23H1、PCNA表达及其相关性研究

THE EXPRESSIONS OF TELOMERASE PROTEIN hTRT GENE,P53,N-ras,nm23H1, PCNA AND THEIR RELATIONSHIP IN SMALL HEPATOCELLULAR CARCINOMA(SHC)

目的 :研究小肝癌中端粒酶蛋白 h TRT基因与 P5 3蛋白、N- ras蛋白、 nm2 3H1蛋白、PCNA表达及其相关性。方法 :在 2 0例小肝癌中用原位杂交 ,免疫组化方法检测 h TRT基因与 P5 3蛋白、N- ras蛋白、nm2 3H1蛋白、PCNA的表达。结果 :h TRT阳性信号检出率 80 % (16 / 2 0 ) ,其余蛋白检出阳性率 P5 3为 35 % (7/ 2 0 ) ,N- ras为90 % (18/ 2 0 ) ,nm 2 3H1为 85 % (17/ 2 0 )及 PCNA强阳性率为 5 5 % (11/ 2 0 ) ;癌中 h TRT阳性信号、P5 3蛋白、PCNA表达强度显著高于癌旁非癌组织 (P<0 .0 5 ) ;癌不同分化组中 P5 3蛋白、nm2 3H1、PCNA表达有显著差异 (P<0 .0 5 ) ;癌中 h TRT阳性信号分布有膜型和浆型两种形式 ,其分布形式、信号强度均与 PCNA阳性强度密切相关 (P<0 .0 1) ,但未检出与 P5 3、N- ras、nm 2 3H1有明显相关性。 nm2 3H1,N- ras在癌与非癌中表达较高。结论 :肝癌发生发展不同阶段有多种基因各自发挥着不同的作用 ,P5 3异常表达是肝癌多基因变化的基础。端粒酶活化发生在肝癌早期 ,是肝细胞增生和恶性转化所必需 ,其检出结果对鉴别肿瘤恶变有重要意义。

Objective:To study the expression of telomerase protein hTRT gene and the protein expressions of P53 ,N-ras ,nm23H1 ,PCNA and their significance in SHC. Methods: In situ hybridization (ISH) and immunohistochemistry technique were used to investigate the expression of telomerase protein hTRT gene and the expressions of ,P53,N-ras ,nm23H1, PCNA in 20 cases of SHC. Results:The expressions of telomerase protein hTRT gene ,P53 protein ,N-ras , nm23H1 ,PCNA in SHC were 80%, 35%, 90%, 85%, and 55%, respectively. The expressions of hTRT , P53 and PCNA in SHC were higher than that in paracarcinoma tissues (P<0.05) .There was a significant difference in the expressions of P53 protein, nm23H1 and PCNA in the different differentiated groups (P<0.05). Two types of hTRT distribution patterns were found, (1) membrance type and (2) cytoplasmic type , whose patterns were positively related with the expression of PCNA , but there was no correlation between hTRT distribution patterns and the expressions of P53 , N-ras , nm23H1. There were higher expressions of N-ras and nm23H1 in SHC and paracarcinoma tissues . Conclusion: There were polygenes playing different roles in the multisteps course of SHC tumorgenesis . The abnormal expression of P53 protein was one of the basement of carceration . Telomerase protein hTRT gene activity was early event in SHC and was considered necessary for liver cell proliferation and malignant transformation, and the detection of hTRT was valuable to clinical oncology diagnosis.