非小细胞肺癌中p16基因异常及其临床病理意义

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

作者信息

Fu Jing, Zhang Jun, Zhang Hong-wei

机构信息

Department of Pathology, Beijing Haidian Hospital, Beijing 100080, China.

出版信息

Zhonghua Bing Li Xue Za Zhi. 2003 Apr;32(2):133-6.

PMID:12839675

Abstract

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.

摘要

目的

探讨非小细胞肺癌（NSCLC）中p16基因mRNA及其蛋白的失活和表达方式及其临床病理意义。

方法

分别采用比较多重聚合酶链反应（PCR）、原位杂交和免疫组织化学方法检测64例NSCLC患者的启动子甲基化状态、mRNA和蛋白表达。

结果

64例NSCLC患者中，36例（56.3%）检测到p16基因启动子甲基化。甲基化阳性结果与免疫组织化学检测的p16蛋白表达呈负相关（P<0.05）。原位杂交显示，13例（20.3%）mRNA呈阳性，所有这些阳性病例（13/13）免疫组织化学也呈阳性。37例（57.8%）免疫组织化学结果为阴性。p16基因启动子甲基化或蛋白表达阴性的NSCLC患者淋巴结转移率较高（P=0.038），3年生存率较低（P=0.002）。