A Re-Emerging Marker for Prognosis in Hepatocellular Carcinoma: The Add-Value of FISHing c-myc Gene for Early Relapse |
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| Authors: | Federica Pedica Andrea Ruzzenente Fabio Bagante Paola Capelli Ivana Cataldo Serena Pedron Calogero Iacono Marco Chilosi Aldo Scarpa Matteo Brunelli Anna Tomezzoli Guido Martignoni Alfredo Guglielmi |
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| Affiliation: | 1. Azienda Ospedaliera Universitaria Integrata di Verona, FISH Molecular Laboratory, Department of Pathology and Diagnostic, University of Verona, Verona, Italy.; 2. Department of Surgery, Division of General Surgery "A", GB Rossi Hospital, University of Verona Medical School, University of Verona, Verona, Italy.; 3. Azienda Ospedaliera Universitaria Integrata di Verona, dO DAI Pathology and Diagnostic, Verona, Italy.; The Chinese University of Hong Kong, Hong Kong, |
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| Abstract: | Hepatocellular carcinoma is one leading cause of cancer-related death and surgical resection is still one of the major curative therapies. Recently, there has been a major effort to find mechanisms involved in carcinogenesis and early relapse. c-myc gene abnormality is found in hepatocarcinogenesis. Our aim was to analyze the role of c-myc as prognostic factor in terms of overall survival and disease-free survival and to investigate if c-myc may be an important target for therapy. We studied sixty-five hepatocellular carcinomas submitted to surgical resection with curative intent. Size, macro-microvascular invasion, necrosis, number of nodules, grading and serum alfa-fetoprotein level were registered for all cases. We evaluated the c-myc aberrations by using break-apart FISH probes. Probes specific for the centromeric part of chromosome 8 and for the locus specific c-myc gene (8q24) were used to assess disomy, gains of chromosomes (polysomy due to polyploidy) and amplification. c-myc gene amplification was scored as 8q24/CEP8 > 2. Statistical analysis for disease-free survival and overall survival were performed. At molecular level, c-myc was amplified in 19% of hepatocellular carcinoma, whereas showed gains in 55% and set wild in 26% of cases. The 1- and 3-year disease-free survival and overall survival for disomic, polysomic and amplified groups were significantly different (p=0.020 and p=.018 respectively). Multivariate analysis verified that the AFP and c-myc status (amplified vs. not amplified) were significant prognostic factors for overall patients survival. c-myc gene amplification is significantly correlated with disease-free survival and overall survival in patients with hepatocellular carcinoma after surgical resection and this model identifies patients with risk of early relapse (≤12 months). We suggest that c-myc assessment may be introduced in the clinical practice for improving prognostication (high and low risk of relapse) routinely and may have be proposed as biomarker of efficacy to anti-c-myc targeted drugs in clinical trials. |
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