ALK基因在肝细胞癌中的表达及临床意义

Anaplastic lymphoma kinase gene expression and its clinical significance in hepatocellular carcinoma

目的探讨间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)基因在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法采用荧光原位杂交法(fluorescent in situ hybridization,FISH)检测ALK在213例HCC组织中的表达,并分析其与患者临床病理特征及预后的相关性。结果 213例HCC中无ALK基因重排阳性,28例存在ALK基因拷贝数增加(ALK gene copy number gain,ALK-CNG)现象。ALK-CNG阳性表达与HCC患者年龄、性别、AJCC分期、Child-Pugh评分及复发情况均无明显相关性(P>0.05),与HCC患者预后相关(P=0.048),晚期患者中ALKCNG阳性组与阴性组的无进展生存率差异有统计学意义(P=0.007)。单变量和多变量Cox回归分析显示,ALK-CNG阳性是HCC患者的独立预后预测指标(P=0.046)。结论 HCC患者ALK基因重排阳性少见,但存在ALK基因拷贝数增加现象,且可能是影响HCC患者预后的不良因素。

Objective To examine the status and clinical significance of anaplastic lymphoma kinase（ALK） gene alterations in hepatocellular carcinoma（HCC） patients. Methods We detected ALK gene expression in HCC tissues using fluorescent in situ hybridization,and we assessed the correlation of ALK gene expression with clinicopathologic outcomes and prognosis in HCC. Results ALK gene translocation was not observed in any HCC cases in the present study. In contrast, gain in ALK gene copy number （ALK-CNG）was detected in 28 HCC patients, and this copy number gain did not positively correlate with age,sex,AJCC stage,recurrence or Child-Pugh classification（P〉0.05）. Copy number gain did positively correlate with poorer prognosis in HCC（P=0.048）,especially among patients with stage Ⅲ/Ⅳ disease（P=0.007）. Univariate and multivariate Cox proportional hazards regression analysis suggested that ALK-CNG was an independent prognostic indicator for patients with HCC（P=0.046）. Conclusion ALK-CNG, but not translocation of ALK,is present in HCC and may predict unfavorable prognosis.