| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Short Communication |
From the Département de Pathologie*
and Service de
Chirurgie,
Hôpital Henri Mondor -
AP-HP, Créteil; and the Unité de Recombinaison et
Expression Génétique,
Institut
National de la Santé et de la Recherche Médicale U163,
Institut Pasteur, Paris, France
Inappropriate activation of the Wnt pathway resulting from ß-catenin gene alterations has recently been implicated in the development of hepatocellular carcinoma (HCC). To explore the in vivo effects of mutated ß-catenin, HCC specimens from 32 patients carrying one or several tumors were screened for somatic mutations in exon 3 of the ß-catenin gene, and the expression and subcellular localization of ß-catenin was studied by immunohistochemistry. Missense mutations or interstitial deletions in ß-catenin exon 3 were detected in 12 of 35 (34%) HCC samples. After immunostaining, most tumors exhibited increased membranous and/or cytoplasmic expression of ß-catenin compared with adjacent nontumoral liver. Strong nuclear accumulation of ß-catenin was observed either focally or uniformly in 15 of 35 (43%) tumor specimens, but not in cirrhotic nodules or dysplastic liver cells in adjacent liver. Aberrant nuclear expression of ß-catenin was significantly associated with the presence of mutations in the ß-catenin gene (P < 0.005). Moreover, nuclear ß-catenin staining correlated significantly with increased Ki-67 proliferative index in tumor (P < 0.001) and seemed to be associated with poor outcome in patients with HCC. In conclusion, our data indicate that activation of the Wnt/ß-catenin pathway in HCC results mainly from somatic mutations in the ß-catenin gene and may promote tumor progression by stimulating tumor cell proliferation.
This article has been cited by other articles:
 |
|
 |
|
  M. Kushida, S. Aiso, K. Morimura, M. Wei, H. Wanibuchi, K. Nagano, and S. Fukushima Absence of {beta}-Catenin Alteration in Hepatic Tumors Induced by p-Nitroanisole in Crj:BDF1 Mice Toxicol Pathol, April 1, 2006; 34(3): 237 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Ellison, O. E. Onilude, J. C. Lindsey, M. E. Lusher, C. L. Weston, R. E. Taylor, A. D. Pearson, and S. C. Clifford {beta}-Catenin Status Predicts a Favorable Outcome in Childhood Medulloblastoma: The United Kingdom Children's Cancer Study Group Brain Tumour Committee J. Clin. Oncol., November 1, 2005; 23(31): 7951 - 7957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yu, P. M. Weinberger, E. Provost, B. G. Haffty, C. Sasaki, J. Joe, R.L. Camp, D.L. Rimm, and A. Psyrri {beta}-Catenin Functions Mainly as an Adhesion Molecule in Patients with Squamous Cell Cancer of the Head and Neck Clin. Cancer Res., April 1, 2005; 11(7): 2471 - 2477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kim, R. C. Sills, and C. D. Houle Overview of the Molecular Biology of Hepatocellular Neoplasms and Hepatoblastomas of the Mouse Liver Toxicol Pathol, January 1, 2005; 33(1): 175 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sharma, A. Pradeep, L. Wong, A. Rana, and B. Rana Peroxisome Proliferator-activated Receptor {gamma} Activation Can Regulate {beta}-Catenin Levels via a Proteasome-mediated and Adenomatous Polyposis Coli-independent Pathway J. Biol. Chem., August 20, 2004; 279(34): 35583 - 35594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Sekhon, X. Tan, A. Micsenyi, W. C. Bowen, and S. P.S. Monga Fibroblast Growth Factor Enriches the Embryonic Liver Cultures for Hepatic Progenitors Am. J. Pathol., June 1, 2004; 164(6): 2229 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fiorentino, A. Altimari, M. Ravaioli, E. Gruppioni, E. Gabusi, B. Corti, M. Vivarelli, P.-P. Bringuier, J.-Y. Scoazec, W. F. Grigioni, et al. Predictive Value of Biological Markers for Hepatocellular Carcinoma Patients Treated with Orthotopic Liver Transplantation Clin. Cancer Res., March 1, 2004; 10(5): 1789 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yang, M. Guo, J. G. Herman, and D. P. Clark Aberrant Promoter Methylation Profiles of Tumor Suppressor Genes in Hepatocellular Carcinoma Am. J. Pathol., September 1, 2003; 163(3): 1101 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Kim and X. W. Wang Gene expression profiling of preneoplastic liver disease and liver cancer: a new era for improved early detection and treatment of these deadly diseases? Carcinogenesis, March 1, 2003; 24(3): 363 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Adam, T. Danciu, D. L. McLellan, J. G. Borer, J. Lin, D. Zurakowski, M. H. Weinstein, P. H. Rajjayabun, J. K. Mellon, and M. R. Freeman A Nuclear Form of the Heparin-binding Epidermal Growth Factor-like Growth Factor Precursor Is a Feature of Aggressive Transitional Cell Carcinoma Cancer Res., January 15, 2003; 63(2): 484 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-M. Tong, U. Cortes, M. P. Hande, H. Ohgaki, L. R. Cavalli, P. M. Lansdorp, B. R. Haddad, and Z.-Q. Wang Synergistic Role of Ku80 and Poly(ADP-ribose) Polymerase in Suppressing Chromosomal Aberrations and Liver Cancer Formation Cancer Res., December 1, 2002; 62(23): 6990 - 6996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kotsinas, K. Evangelou, P. Zacharatos, C. Kittas, and V. G. Gorgoulis Proliferation, but Not Apoptosis, Is Associated with Distinct {beta}-Catenin Expression Patterns in Non-Small-Cell Lung Carcinomas : Relationship with Adenomatous Polyposis Coli and G1-to S-Phase Cell-Cycle Regulators Am. J. Pathol., November 1, 2002; 161(5): 1619 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R J Campbell and M Pignatelli Molecular histology in the study of solid tumours Mol. Pathol., April 1, 2002; 55(2): 80 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. S. Monga, W. M. Mars, P. Pediaditakis, A. Bell, K. Mule, W. C. Bowen, X. Wang, R. Zarnegar, and G. K. Michalopoulos Hepatocyte Growth Factor Induces Wnt-independent Nuclear Translocation of {beta}-Catenin after Met-{beta}-Catenin Dissociation in Hepatocytes Cancer Res., April 1, 2002; 62(7): 2064 - 2071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Abraham, T.-T. Wu, R. H. Hruban, J.-H. Lee, C. J. Yeo, K. Conlon, M. Brennan, J. L. Cameron, and D. S. Klimstra Genetic and Immunohistochemical Analysis of Pancreatic Acinar Cell Carcinoma : Frequent Allelic Loss on Chromosome 11p and Alterations in the APC/{beta}-Catenin Pathway Am. J. Pathol., March 1, 2002; 160(3): 953 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Inagawa, M. Itabashi, S. Adachi, T. Kawamoto, M. Hori, J. Shimazaki, F. Yoshimi, and K. Fukao Expression and Prognostic Roles of {beta}-Catenin in Hepatocellular Carcinoma: Correlation with Tumor Progression and Postoperative Survival Clin. Cancer Res., February 1, 2002; 8(2): 450 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Chung, E. Provost, E. P. Kielhorn, L. A. Charette, B. L. Smith, and D. L. Rimm Tissue Microarray Analysis of {beta}-Catenin in Colorectal Cancer Shows Nuclear Phospho-{beta}-catenin Is Associated with a Better Prognosis Clin. Cancer Res., December 1, 2001; 7(12): 4013 - 4020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shiina, M. Igawa, S. Urakami, K. Shigeno, T. Yoneda, M. Terashima, M. Deguchi, L. Ribeiro-Filho, and R. Dahiya Alterations of {beta}- and {gamma}-Catenin in N-Butyl-N-(-4-hydroxybutyl)nitrosamine-induced Murine Bladder Cancer Cancer Res., October 1, 2001; 61(19): 7101 - 7109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R T Pirinen, P Hirvikoski, R T Johansson, S Hollmen, and V-M Kosma Reduced expression of {{alpha}}-catenin, {beta}-catenin, and {{gamma}}-catenin is associated with high cell proliferative activity and poor differentiation in non-small cell lung cancer J. Clin. Pathol., May 1, 2001; 54(5): 391 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cadoret, C. Ovejero, S. Saadi-Kheddouci, E. Souil, M. Fabre, B. Romagnolo, A. Kahn, and C. Perret Hepatomegaly in Transgenic Mice Expressing an Oncogenic Form of {beta}-Catenin Cancer Res., April 1, 2001; 61(8): 3245 - 3249. [Abstract] [Full Text]
|
|
|
|
|
|
D. F. Calvisi, V. M. Factor, R. Loi, and S. S. Thorgeirsson Activation of {beta}-Catenin during Hepatocarcinogenesis in Transgenic Mouse Models: Relationship to Phenotype and Tumor Grade Cancer Res., March 1, 2001; 61(5): 2085 - 2091. [Abstract] [Full Text]
|
|
|
|
|
|
G. Garcia-Rostan, R. L. Camp, A. Herrero, M. L. Carcangiu, D. L. Rimm, and G. Tallini {beta}-Catenin Dysregulation in Thyroid Neoplasms : Down-Regulation, Aberrant Nuclear Expression, and CTNNB1 Exon 3 Mutations Are Markers for Aggressive Tumor Phenotypes and Poor Prognosis Am. J. Pathol., March 1, 2001; 158(3): 987 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M J Pukkila, J A Virtaniemi, E J Kumpulainen, R T Pirinen, R T Johansson, H J Valtonen, M T Juhola, and V-M Kosma Nuclear {beta} catenin expression is related to unfavourable outcome in oropharyngeal and hypopharyngeal squamous cell carcinoma J. Clin. Pathol., January 1, 2001; 54(1): 42 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Polakis Wnt signaling and cancer Genes & Dev., August 1, 2000; 14(15): 1837 - 1851. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
