title: A re-emerging marker for prognosis in hepatocellular carcinoma: the add-value of fishing c-myc gene for early relapse.
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.
authors.affiliation: Azienda Ospedaliera Universitaria Integrata di Verona, FISH Molecular Laboratory, Department of Pathology and Diagnostic, University of Verona, Verona, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pedica
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruzzenente
authors.forename: Fabio
authors.initials: F
authors.lastname: Bagante
authors.forename: Paola
authors.initials: P
authors.lastname: Capelli
authors.forename: Ivana
authors.initials: I
authors.lastname: Cataldo
authors.forename: Serena
authors.initials: S
authors.lastname: Pedron
authors.forename: Calogero
authors.initials: C
authors.lastname: Iacono
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.forename: Anna
authors.initials: A
authors.lastname: Tomezzoli
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.forename: Alfredo
authors.initials: A
authors.lastname: Guglielmi
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D016259:Genes, myc / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor