title: Wnt/beta-catenin signaling pathway in hepatocellular carcinomas cases from Colombia.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is the most common primary liver cancer diagnosed worldwide. Deregulation of Wnt/beta-catenin pathway has been associated with the development of HCC in a substantial number of cases in Europe and far less in Asia. Nothing is known about this pathway in HCC cases from South America. This study aimed to investigate the frequency of mutations in beta-catenin gene (CTNNB1) and the subcellular localization of beta-catenin in HCC cases from Colombia.
  
  
  METHODS
  We determine by direct sequencing the frequency of mutations in exon 3 of CTNNB1 gene and by immunohistochemistry the subcellular localization of beta-catenin in 54 samples of HCC obtained from three pathology units in Bogota and Medellin cities.
  
  
  RESULTS
  Only three HCC cases (5.6%) were found mutated at residues (G34E, S45P, P44S, T41I) important for phosphorylation and ubiquitination of beta-catenin protein. Strikingly, nuclear or cytoplasmic accumulation of beta-catenin, hallmark of Wnt pathway activation, was found in 42.6% HCC cases (23/54). Interestingly, beta-catenin accumulation was significantly more frequent in young patients and hepatitis B virus-related HCC.
  
  
  CONCLUSIONS
  Although, CTNNB1 exon 3 mutations are not frequent in HCC from Colombian patients, our findings indicate that Wnt/beta-catenin signaling is activated in 42.6% of HCC samples. Furthermore, Wnt signaling was demonstrated in HCC cases associated of HBV infection, one of the most important HCC risk factors in Colombia.
authors.affiliation: Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, UdeA, Medellin, Colombia.
authors.forename: Iris
authors.initials: I
authors.lastname: Suarez M
authors.affiliation: Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, UdeA, Medellin, Colombia.
authors.forename: Diego
authors.initials: D
authors.lastname: Uribe
authors.affiliation: Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, UdeA, Medellin, Colombia.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Jaramillo
authors.affiliation: Grupo de Gastrohepatologia, Departamento de Patologia. Facultad de Medicina, Universidad de Antioquia, UdeA, Medellin, Colombia.
authors.forename: German
authors.initials: G
authors.lastname: Osorio
authors.affiliation: Hospital Pablo Tobon Uribe, Medellin, Colombia.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Perez
authors.affiliation: Departamento de Patologia, Fundacion Santa Fe de Bogota, Bogota, Colombia.
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.affiliation: Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, UdeA, Medellin, Colombia.
authors.forename: Sergio
authors.initials: S
authors.lastname: Hoyos
authors.affiliation: International Prevention Research Institute, Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.affiliation: Unité Organisation Nucleaire et Oncogènese, INSERM U993, Institut Pasteur, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pineau
authors.affiliation: Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, UdeA, Medellin, Colombia.
authors.forename: Maria-C
authors.initials: MC
authors.lastname: Navas
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D003105:Colombia; D005091:Exons; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D012189:Retrospective Studies; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin