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For: Thunnissen E, Bubendorf L, Dietel M, Elmberger G, Kerr K, Lopez-Rios F, Moch H, Olszewski W, Pauwels P, Penault-Llorca F. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch. 2012;461:245-257. [PMID: 22825000 DOI: 10.1007/s00428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

For:	Thunnissen E, Bubendorf L, Dietel M, Elmberger G, Kerr K, Lopez-Rios F, Moch H, Olszewski W, Pauwels P, Penault-Llorca F. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch. 2012;461:245-257. [PMID: 22825000 DOI: 10.1007/s00428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

Number	Cited by Other Article(s)
1	Jia SW, Fu S, Wang F, Shao Q, Huang HB, Shao JY. ALK gene copy number gain and its clinical significance in hepatocellular carcinoma. World J Gastroenterol 2014;20:183-192. [PMID: 24415871 PMCID: PMC3886007 DOI: 10.3748/wjg.v20.i1.183] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 10/08/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open 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 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. Collapse Key Words Anaplastic lymphoma kinase gene Hepatocellular carcinoma Prognostic predictor Collapse MESH Headings Adult Aged Anaplastic Lymphoma Kinase Biomarkers, Tumor/analysis Biomarkers, Tumor/genetics Carcinoma, Hepatocellular/enzymology Carcinoma, Hepatocellular/genetics Carcinoma, Hepatocellular/mortality Carcinoma, Hepatocellular/pathology Chi-Square Distribution DNA Copy Number Variations Disease Progression Disease-Free Survival Female Gene Dosage Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease Humans Immunohistochemistry In Situ Hybridization, Fluorescence Kaplan-Meier Estimate Liver Neoplasms/enzymology Liver Neoplasms/genetics Liver Neoplasms/mortality Liver Neoplasms/pathology Male Middle Aged Multivariate Analysis Neoplasm Grading Neoplasm Staging Phenotype Proportional Hazards Models Receptor Protein-Tyrosine Kinases/analysis Receptor Protein-Tyrosine Kinases/genetics Retrospective Studies Risk Factors Time Factors Tissue Array Analysis Collapse Grants Collapse Affiliation(s) Collapse

Number

Cited by Other Article(s)

Jia SW, Fu S, Wang F, Shao Q, Huang HB, Shao JY. ALK gene copy number gain and its clinical significance in hepatocellular carcinoma. World J Gastroenterol 2014;20:183-192. [PMID: 24415871 PMCID: PMC3886007 DOI: 10.3748/wjg.v20.i1.183] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 10/08/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open

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 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.

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