Shou-Wei Jia, Hong-Bing Huang, Department of Pharmacy, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center on Cancer Medicine; Guangzhou 510060, Guangdong Province, China.
World J Gastroenterol. 2014 Jan 7;20(1):183-92. doi: 10.3748/wjg.v20.i1.183.
To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients.
A total of 213 cases of HCC were examined by fluorescent in situ hybridization using dual color break-apart ALK probes for the detection of chromosomal translocation and gene copy number gain. HCC tissue microarrays were constructed, and the correlation between the ALK status and clinicopathological variables was assessed by χ(2) test or Fisher's exact test. Survival analysis was estimated using the Kaplan-Meier approach with a Log-rank test. Univariate and multivariate analyses of clinical variables were performed using the Cox proportional hazards regression model.
ALK gene translocation was not observed in any of the HCC cases included in the present study. ALK gene copy number gain (ALK/CNG) (≥ 4 copies/cell) was detected in 28 (13.15%) of the 213 HCC patients. The 3-year progression-free-survival (PFS) rate for ALK/CNG-positive HCC patients was significantly poorer than ALK/CNG-negative patients (27.3% vs 42.5%, P = 0.048), especially for patients with advanced stage III/IV (0% vs 33.5%, P = 0.007), and patients with grade III disease (24.8% vs 49.9%, P = 0.023). ALK/CNG-positive HCC patients had a significantly poorer prognosis than ALK/CNG-negative patients in the subgroup that was negative for serum hepatitis B virus DNA, with significantly different 3-year overall survival rates (18.2% vs 63.6%, P = 0.021) and PFS rates (18.2% vs 46.9%, P = 0.019). Multivariate Cox proportional hazards regression analysis suggested that ALK/CNG prevalence can predict death in HCC (HR = 1.596; 95%CI: 1.008-2.526, P = 0.046).
ALK/CNG, but not translocation of ALK, is present in HCC and may be an unfavorable prognostic predictor.
检测间变性淋巴瘤激酶（ALK）基因改变在肝细胞癌（HCC）患者中的状态和临床意义。
采用双色断裂分离 ALK 探针的荧光原位杂交技术检测 213 例 HCC 患者的染色体易位和基因拷贝数增加。构建 HCC 组织微阵列，通过 χ(2)检验或 Fisher 确切检验评估 ALK 状态与临床病理变量的相关性。采用 Kaplan-Meier 法和 Log-rank 检验进行生存分析。采用 Cox 比例风险回归模型进行临床变量的单因素和多因素分析。
本研究中未观察到任何 HCC 病例存在 ALK 基因易位。在 213 例 HCC 患者中，有 28 例（13.15%）检测到 ALK 基因拷贝数增加（ALK/CNG）（≥ 4 拷贝/细胞）。ALK/CNG 阳性 HCC 患者的 3 年无进展生存率（PFS）明显低于 ALK/CNG 阴性患者（27.3% vs 42.5%，P = 0.048），尤其是晚期 III/IV 期（0% vs 33.5%，P = 0.007）和 III 级疾病患者（24.8% vs 49.9%，P = 0.023）。在乙型肝炎病毒 DNA 阴性的亚组中，ALK/CNG 阳性 HCC 患者的预后明显差于 ALK/CNG 阴性患者，3 年总生存率（18.2% vs 63.6%，P = 0.021）和 PFS 率（18.2% vs 46.9%，P = 0.019）存在显著差异。多因素 Cox 比例风险回归分析表明，ALK/CNG 发生率可预测 HCC 患者的死亡（HR = 1.596；95%CI：1.008-2.526，P = 0.046）。
ALK/CNG 而非 ALK 易位存在于 HCC 中，可能是一个不利的预后预测指标。
