p16基因启动子甲基化与结直肠癌发生发展的关系

目的　探讨p16基因启动子甲基化在结直肠癌发生、发展过程中的作用及其临床意义。方法　采用RT PCR、免疫组化方法检测p16基因表达 ,用甲基化特异性PCR(MSP)方法检测p16基因启动子甲基化。结果　 5 8例结直肠癌中 ,癌旁肠粘膜、原发灶、肝转移灶中p16表达阳性率分别为97% (5 6 /5 8)、31% (18/5 8)、7% (2 /2 8) ,原发灶、肝转移灶中p16表达明显降低 (P <0 0 1)。癌旁肠粘膜组织中未发现p16基因启动子甲基化 ,而癌原发灶、肝转移灶中p16甲基化阳性率分别为 5 0 %(2 9/5 8)、75 % (2 1/2 8) ,3种组织p16基因启动子甲基化率的差别有显著性意义 (P <0 0 1)。在 2 8例出现肝转移者外周静脉血、胆汁中可检测到p16甲基化启动子序列者分别为 2 3例 (82 % )、2 0例 (71% )。结论　p16基因启动子甲基化导致p16抑癌基因失活与结直肠癌的发生、转移有密切关系。

Methylation of p16 gene in promotor region is related with the genesis and progress of colorectal cancer

Objective To study the correlation between methylation of p16 gene in promotor region with the genesis and progress of colorectal cancer. Methods Methylation-specific PCR was used to detect methylation of p16 promotor region.Expression of p16 was examined by RT-PCR and immunohistochemistry techniques. Results In 58 cases of colorectal cancer, p16 expression was detected in 97%(56/58), 31%(18/58), and 7%(2/28) in paratumoral mucous membrana, primary cancer foci and hepatic metastasis respectively. p16 expression in primary foci and hepatic metastasis was lower than that in paratumoral mucous membrana (P<0.01). Methylation of p16 promotor in primary foci and hepatic metastasis was found in 29/58(50%), and 21/28(75%)(P<0.01).No methylation was found in paratumour mucous membrana. In 28 cases of hepatic metastasis, 23(82%) were found with p16 promotor methylation sequence in the venous blood, and 20(71%) in bile. Conclusion Methylation of p16 promotor leads to inhibition of p16 gene, genesis and metastasis of colorectal cancer.