肝细胞癌中p16基因及其甲基化的检测与意义

目的　研究P16、P16甲基化在肝细胞癌 (Hepatocellularcarcinoma ,HCC)与癌旁组织中的表达特点 ,探讨其与HCC生物学行为的关系。方法　分别以免疫组化及PCR技术检测 3 3例人肝细胞癌及其癌旁组织中p16基因表达及其甲基化的水平 ,并结合临床资料进行分析。结果　肝癌的p16基因表达率 (63 64 % )明显低于癌旁组织 (10 0 % ) (P <0 0 5 ) ;p16基因阳性表达率在无转移的肝癌中为 85 7% ,有转移组为 2 5 0 % ;高、中和低分化的肝癌分别为 5 2 4% ,2 8 6%和 19 1%。p16基因阳性表达在肝癌患者高分化与中和低分化比较有显著性差异 (P <0 0 5 ) ,转移与非转移组比较有非常显著性差异 (P <0 0 1)。 3 3例HCC组织中 11例发生p16甲基化 ,均伴肿瘤转移 ,其中高、中和低分化肿瘤各占 2、4、5例 ;相应癌旁组织中未发现p16基因甲基化。结论　p16基因异常表达及其甲基化在肝细胞癌的发生、发展过程中起重要作用。

Detection and significance of p16 and its methylation in primary hepatocellular carcinoma

Objective To investigate p16 gene expression and its methylation in primary hepatocellular carcinoma (HCC) and in the corresponding tumor adjacent tissues, and evaluate their significance in biological behaviors of the tumor. Methods Immunohistochemical and PCR based methylation analysis were performed on 33 HCC samples and their corresponding tumor adjacent specimens for p16 and its methylation. Results The expression of p16 was much lower in tumor tissues (63.64%) than tumor adjacent tissues (100%) ( P <0.05). The positive expression of p16 was 25.0% in the carcinoma with metastasis and 85.7% without metastasis. p16 gene expression in highly, moderately and poorly differentiated HCC was 52.4%, 28.6% and 19.1% respectively,with an obvious difference between highly differentiated and poorly differentiated HCC ( P <0.05),and between groups with and without metastasis ( P <0.01). Methylation of p16 was found in 11/33 samples obtained from the metastatic tumors, including highly differentiated (2), moderately differentiated (4) and poorly differentiated HCC (5). However, no methylation of p16 was detected in all the tumor adjacent tissues. Conclusion Methylation of p16 may be one of the main mechanisms of the inactivation of P16 protein and play an important role in the genesis and progression of HCC.