HBsAg阳性肝癌患者预后及病理因素与ALK基因表达的相关性研究

 目的:检测ALK基因在HBsAg阳性肝细胞癌患者中的表达,并分析其与临床特征及预后的相关性。方法:收集我院2005~2010年261例术后经病理确诊的HBsAg阳性肝癌患者肿瘤组织及癌旁组织标本,采用免疫组织化学法和FISH法对标本石蜡切片进行分析,检测ALK表达情况,并探讨其对HBsAg阳性肝癌患者临床病理因素和预后的影响。结果:在肿瘤组织中,免疫组织化学法和FISH法分别检测到ALK阳性表达率为44.8%和32.6%。免疫组化结果进一步显示ALK蛋白表达与患者性别、肿瘤数目和微转移密切相关(P<0.05),而与患者的年龄、AFP水平、肿瘤大小、临床分期等无关;ALK阳性患者总生存期和无进展生存期均明显低于阴性患者(P<0.01);多因素分析显示,ALK表达和微转移是对患者无进展生存期具有统计学显著性的预后因素。结论:ALK在HBsAg阳性肝癌组织表达状态与肝癌的生长和转移关系密切,可以作为反映肝癌生物学行为和判断预后的有效指标。

Status and clinical significance of ALK gene expression in HBsAg-positive hepatocellular carcinoma patients

AIM: To detect the status of anaplastic lymphoma kinase (ALK) in the HBsAg-positive hepatocellular carcinoma (HCC) patients, and to investigate the relationship between ALK gene expression or clinical features or prognosis.METHODS: The surgical patients with HBsAg-positive HCC (n=261) were followed up for at least 2 years. The expression of ALK was examined by the methods of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in their archival paraffin embedded tissue specimens, and it was statistically analyzed whether ALK gene abnormalities were associated with patients' clinical features. RESULTS: Over-expression of ALK protein and ALK gene copy number gain were 44.8% observed by IHC and 32.6% by FISH. The expression of ALK was highly correlated with gender, tumor multiplicity and micrometastasis (P<0.05), but not with age, AFP, tumor size, clinical stage, etc. The survival rate in the patients with positive ALK expression was much lower than that in the patients with negative ALK expression (P<0.01). Multivariate analysis indicated that ALK expression and micrometastasis were both significant prognostic factors of HCC. CONCLUSION: Over-expression of ALK in HBsAg-positive HCC tissues increases the possibilities of growth and metastasis, and ALK may serve as fairly a good indicator for biologic behavior and prognosis of HCC.