Shou-Wei Jia1, Sha Fu1, Fang Wang1, Qiong Shao1, Hong-Bing Huang1, Jian-Yong Shao1. 1. 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.
Abstract
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 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. 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.
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 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. 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.
Authors: Marta Salido; Lara Pijuan; Luz Martínez-Avilés; Ana B Galván; Israel Cañadas; Ana Rovira; Montserrat Zanui; Alejandro Martínez; Raquel Longarón; Francisco Sole; Sergio Serrano; Beatriz Bellosillo; Murry W Wynes; Joan Albanell; Fred R Hirsch; Edurne Arriola Journal: J Thorac Oncol Date: 2011-01 Impact factor: 15.609
Authors: Matthias Preusser; Anna S Berghoff; Ayseguel Ilhan-Mutlu; Manuel Magerle; Carina Dinhof; Georg Widhalm; Karin Dieckmann; Christine Marosi; Adelheid Wöhrer; Monika Hackl; Sabine Zöchbauer-Müller; Andreas von Deimling; Sebastian F Schoppmann; Christoph C Zielinski; Berthold Streubel; Peter Birner Journal: Lung Cancer Date: 2013-02-27 Impact factor: 5.705
Authors: M Łastowska; V Viprey; M Santibanez-Koref; I Wappler; H Peters; C Cullinane; P Roberts; A G Hall; D A Tweddle; A D J Pearson; I Lewis; S A Burchill; M S Jackson Journal: Oncogene Date: 2007-05-28 Impact factor: 9.867
Authors: Fang Wang; Thomas Bank; Gregory Malnassy; Maribel Arteaga; Na Shang; Annika Dalheim; Xianzhong Ding; Scott J Cotler; Mitchell F Denning; Michael I Nishimura; Peter Breslin; Wei Qiu Journal: Hepatol Commun Date: 2018-04-17
Authors: U Peretti; R Ferrara; S Pilotto; S Kinspergher; M Caccese; A Santo; M Brunelli; A Caliò; L Carbognin; I Sperduti; M Garassino; M Chilosi; A Scarpa; G Tortora; E Bria Journal: Respir Res Date: 2016-08-25