非小细胞肺癌p16基因异常与临床病理相关性研究

目的　探讨抑癌基因p16在非小细胞肺癌中的失活方式、mRNA和p16蛋白表达与临床病理因素的相关性。方法　应用对比性多重聚合酶链式反应检测 6 4例非小细胞肺癌中p16基因启动子的甲基化状况 ,同时应用原位杂交和免疫组织化学方法 链霉素抗生物素蛋白 过氧化物酶 (SP)法 ]检测p16基因的mRNA和蛋白表达水平 ,并将上述结果与非小细胞肺癌之临床病理因素进行了相关性研究。结果　 5 6 3% (36 / 6 4 )的肺癌标本被检出有p16基因启动子甲基化 ,且甲基化与p16蛋白表达呈负相关 (P <0 0 5 ) ;免疫组织化学检测结果显示 ,5 7 8% (37/ 6 4 )的标本呈现p16蛋白表达缺失 ;原位杂交检测有 2 0 3% (13/ 6 4 )的标本被检出p16mRNA表达 ,且这 13例阳性者的p16蛋白也表达。同时具有p16基因启动子甲基化和蛋白表达缺失的非小细胞肺癌患者淋巴结转移率明显增高 ,术后生存期明显降低 (P <0 0 5 )。结论　启动子甲基化是导致非小细胞肺癌p16基因失活的主要方式 ,同时具有p16基因启动子甲基化及p16蛋白表达异常的患者预后不良

Abnormality of p16 gene and its clinicopathological significance in non-small cell lung cancer

Objective To investigate the ways of inactivation and expression of p16 gene mRNA and its protein as well, and their clinicopathological significance in non small cell lung carcinomas (NSCLC) Methods Comparative multiplex PCR, in situ hybridization, and immunohistochemistry were used to detect the promotor methylation status, mRNA, and protein expression in 64 cases of NSCLC, respectively Results Promoter methylation of p16 gene was detected in 36 (56 3%) of 64 NSCLC cases This positive result of methylation showed a negative correlation statistically with p16 protein expression by immunohistochemistry ( P <0 05) By in situ hybridization, 13 cases (20 3%) showed positive results for mRNA and all of these positive cases (13/13) had also a positive result by immunohistochemistry Thirty seven cases (57 8%) showed a negative immunohistochemical result The metastatic rate of lymph nodes of those NSCLC patients with either promoter methylation or negative protein expression was higher ( P =0 038), and 3 year survival rate was lower statistically ( P =0 002) Conclusion Dysfunction of p16 gene in NSCLC is mainly caused by promoter methylation, and patients with p16 gene dysfunction may have a poor prognosis