Iris Suarez M1, Diego Uribe1, Carlos M Jaramillo1, German Osorio2, Juan C Perez3, Rocio Lopez4, Sergio Hoyos1, Pierre Hainaut5, Pascal Pineau6, Maria-C Navas1. 1. Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, UdeA, Medellin, Colombia. 2. Grupo de Gastrohepatologia, Departamento de Patologia. Facultad de Medicina, Universidad de Antioquia, UdeA, Medellin, Colombia. 3. Hospital Pablo Tobon Uribe, Medellin, Colombia. 4. Departamento de Patologia, Fundacion Santa Fe de Bogota, Bogota, Colombia. 5. International Prevention Research Institute, Lyon, France. 6. Unité Organisation Nucleaire et Oncogènese, INSERM U993, Institut Pasteur, Paris, France.
Abstract
BACKGROUND AND AIM: 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. MATERIAL AND 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.
BACKGROUND AND AIM: 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. MATERIAL AND 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: Emmet J Jordan; Olca Basturk; Jinru Shia; David S Klimstra; William Alago; Michael I D'Angelica; Ghassan K Abou-Alfa; Eileen M O'Reilly; Maeve A Lowery Journal: J Gastrointest Oncol Date: 2017-10