Published online Jan 7, 2014. doi: 10.3748/wjg.v20.i1.183
Revised: October 8, 2013
Accepted: October 17, 2013
Published online: January 7, 2014
AIM: To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients.
METHODS: 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 χ2 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.
RESULTS: 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).
CONCLUSION: ALK/CNG, but not translocation of ALK, is present in HCC and may be an unfavorable prognostic predictor.
Core tip: This study retrospectively analyzed the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in a relatively large number of hepatocellular carcinoma (HCC) patients. We used HCC tissue microarrays to detect ALK transcripts by fluorescent in situ hybridization. No positive cases of ALK gene rearrangements and ALK amplification were observed. However, we found that ALK gene copy number gain (ALK/CNG) was common in HCC (13.15%, 28/213). Our findings suggest that ALK/CNG may serve as a prognostic marker for HCC, especially in patients with advanced stage, grade III pathology.