Online citations, reference lists, and bibliographies.
← Back to Search

Tumor Heterogeneity In Small Hepatocellular Carcinoma: Analysis Of Tumor Cell Proliferation, Expression And Mutation Of P53 AND β‐catenin

F. An, M. Matsuda, H. Fujii, R. F. Tang, H. Amemiya, Y. Dai, Y. Matsumoto
Published 2001 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Most hepatocellular carcinomas (HCCs) first occur as well‐differentiated HCCs, from which poorly differentiated HCC cells develop because of dedifferentiation. In this study, we try to clarify the changes of dedifferentiation and cell proliferative activity and their relationship in small HCCs (less than 3.0 cm in diameter) and try to learn the mechanism of these changes by analysing the expressions and genetic changes of proliferation‐related genes p53 and β‐catenin. Of 41 surgically resected small HCCs, 11 were identified to have tumor heterogeneity. DNA from the 11 small HCCs, consisting of 29 intratumoral lesions and 11 noncancerous liver tissues adjacent to HCCs, was extracted from paraffin embedded tissue sections. Exons 5–8 of p53 gene and exon 3 of β‐catenin gene were amplified by polymerase chain reaction and analyzed by direct sequence. The serial sections were also immunostained by anti‐Ki‐67, p53 and β‐catenin antibody. Immunohistochemistry showed that the p53 overexpression was significantly related to the proliferative activities as evaluated by Ki‐67 immunostaining and to the histological differentiation. The expression of β‐catenin was found to be heterogeneously distributed not only in various histological grades of the same tumor but also in areas of the same histological grade. p53 and β‐catenin gene mutations were detected in 1 tumor respectively, both of which were second primary HCCs and also recurred later. The p53 mutation showed the same mutation pattern in heterogeneous subpopulations. β‐catenin mutation was detected only in the less differentiated lesion but not in the well‐differentiated lesion of tumor. In conclusion, our findings suggest that there was histological heterogeneity in small but established HCC, which was accompanied by increased proliferative activity and p53 overexpression. The overexpression of β‐catenin may be related to the proliferative activity and dedifferentiation of HCC. © 2001 Wiley‐Liss, Inc.
This paper references
b-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection
H Huang (1999)
Tumor progression in hepatocellular carcinoma may be mediated by p53 mutation.
S. Tanaka (1993)
E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton
J. Huelsken (1994)
Mutation pattern of the p53 gene as a diagnostic marker for multiple hepatocellular carcinoma.
T. Oda (1992)
b-catenin mutations in human prostate cancer
HJ Voeller (1998)
β‐Catenin Accumulation and Mutation of Exon 3 of the β‐Catenin Gene in Hepatocellular Carcinoma
Y. Kondo (1999)
Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver. Observations in five cases.
M. Arakawa (1986)
p53 gene mutations and protein accumulation in human ovarian cancer.
J. Kupryjanczyk (1993)
Mechanisms of tumor progression.
P. Nowell (1986)
p53: oncogene or anti-oncogene?
D. Lane (1990)
Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene.
A. Koch (1999)
Pathomorphologic characteristics of small hepatocellular carcinoma: A special reference to small hepatocellular carcinoma with indistinct margins
O. Nakashima (1995)
Signal transduction by-catenin
BM Gumbiner (1995)
Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3.
Y. Miyoshi (1998)
Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
P. Morin (1997)
Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma.
G. Garcia-Rostan (1999)
Signal transduction of beta-catenin.
B. Gumbiner (1995)
The molecular genetics of cancer.
J. Bishop (1987)
b-catenin accumulation and mutation of exon 3 of the b-catenin gene in hepatocellular carcinoma
Y Kondo (1999)
p53: oncogene or anti-oncogene? Genes Dev 1990;4:1–8
DP Lane (1990)
Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma.
M. Sakamoto (1991)
The clinical significance of p53 gene mutation in hepatocellular carcinomas from japan
H. Hayashi (1995)
A genetic model for colorectal tumorigenesis
E. Fearon (1990)
E-cadherin and APC compete for the interaction withb-catenin and cytoskeleton
J Hulsken (1994)
Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies
H. Edmondson (1954)
High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma.
E. Cesarman (1993)
Expression of p53 gene in 184 unifocal hepatocellular carcinomas: association with tumor growth and invasiveness.
H. Hsu (1993)
Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC.
K. Kenmochi (1987)
Beta-catenin mutations are more frequent in small colorectal adenomas than in larger adenomas and invasive carcinomas.
W. Samowitz (1999)
β-Catenin Mutations in Human Prostate Cancer
H. J. Voeller (1998)
The p53 tumour suppressor gene
A. Levine (1991)
Tumor heterogeneity.
Gloria H. Heppner (1984)
Molecular Analysis of Cancer
J. Crocker (2002)
Identification of p53 as a sequence-specific DNA-binding protein
S. Kern (1991)
Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex Assembly
B. Rubinfeld (1996)
Mutations in the β-Catenin Gene (CTNNB1) in Endometrioid Ovarian Carcinomas
J. Palacios (1998)
Alteration ofb-catenin-Tcf signaling in colon cancer by mutations in b-catenin or APC
PJ Morin (1997)
E-cadherin and APC compete for the interaction with ␤-catenin and cytoskeleton
J Hulsken (1994)
Mutagenic activity of tumor-associated macrophages in Salmonella typhimurium strains TA98 and TA 100.
A. Fulton (1984)
β-Catenin Mutations Are Frequent in Human Hepatocellular Carcinomas Associated with Hepatitis C Virus Infection
Huatao Huang (1999)
Primary carcinoma of the liver: a study of 100 cases among 48,900 hecropsies
HA Edmondson (1954)
Activation of theb-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon
Y Miyoshi (1998)
Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC
剣持 邦彦 (1987)
How a Growth Control Path Takes a Wrong Turn to Cancer
E. Pennisi (1998)
Immunohistochemical detection of aberrant p53 expression in hepatocellular carcinoma: correlation with cell proliferative activity indices, including mitotic index and MIB-1 immunostaining.
T. Nagao (1995)

This paper is referenced by
Tumor Heterogeneity in Hepatocellular Carcinoma: Facing the Challenges
L. Lu (2016)
Immunohistochemical Determination of p53 Protein Overexpression for Predicting p53 Gene Mutations in Hepatocellular Carcinoma: A Meta-Analysis
J. Liu (2016)
Prognostic factors affecting postoperative survival of patients with solitary small hepatocellular carcinoma
Mu-Yan Cai (2016)
Immunohistochemical analysis of p53, cyclinD1, RB1, c-fos and N-ras gene expression in hepatocellular carcinoma in Iran
S. Moghaddam (2007)
Clinical significance of microRNA-21 expression in disease progression of patients with hepatocellular carcinoma.
J. Yoon (2018)
Characterization of hepatocellular carcinoma recurrence after liver transplantation: perioperative prognostic factors, patterns, and outcome.
Kun-Ming Chan (2011)
Intratumor heterogeneity in hepatocellular carcinoma Running title : Implications for tumor classifications and targeted therapies
Juliane (2018)
Orthotopic Implantation of Human Hepatocellular Carcinoma in Mice
C. Armengol (2004)
Genetic alterations in cancer knowledge system: analysis of gene mutations in mouse and human liver and lung tumors.
M. Jackson (2006)
Krüppel-like Factor 4 Blocks Hepatocellular Carcinoma Dedifferentiation and Progression through Activation of Hepatocyte Nuclear Factor-6
H. Sun (2015)
The Improvement of Irreversible Electroporation Therapy Using Saline-Irrigated Electrodes: A Theoretical Study
Oyinlolu O. Adeyanju (2011)
Liver transplantation for hepatocellular carcinoma.
A. Hemming (2001)
Intratumor Heterogeneity in Hepatocellular Carcinoma
J. Friemel (2014)
Beta‐catenin accumulation in the progression of human hepatocarcinogenesis correlates with loss of E‐cadherin and accumulation of p53, but not with expression of conventional WNT‐1 target genes
W. Prange (2003)
Erratum to “Spectrum of molecular changes during hepatocarcinogenesis induced by DEN and other chemicals in Fischer 344 male rats” [Mechanisms of Ageing and Development 123 (2002) 1665–1680]
I. Lim (2003)
Continuum descriptions of spatial spreading for heterogeneous cell populations: theory and experiment.
O. Matsiaka (2019)
Hepatocellular carcinoma pathogenesis: from genes to environment
Paraskevi A. Farazi (2006)
Tumour Size and Differentiation in Predicting Recurrence of Hepatocellular Carcinoma After Liver Transplantation: External Validation of a New Prognostic Score
L. Marelli (2008)
Transmembrane receptor CXCR7 increases the risk of extrahepatic metastasis of relatively well-differentiated hepatocellular carcinoma through upregulation of osteopontin.
T. Xue (2013)
CT texture analysis of pancreatic cancer
K. Sandrasegaran (2018)
Preoperative Assessment of Hepatocellular Carcinoma Tumor Grade Using Needle Biopsy: Implications for Transplant Eligibility
T. Pawlik (2007)
Genome-wide discovery and validation of diagnostic DNA methylation-based biomarkers for hepatocellular cancer detection in circulating cell free DNA
R. Hlady (2019)
Acute Tumor Transition Angle on Computed Tomography Predicts Chromosomal Instability Status of Primary Gastric Cancer: Radiogenomics Analysis from TCGA and Independent Validation
Y. Lai (2019)
Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation
Christin Bürger (2019)
FDG PET/CT and enhanced CT imaging of tumor heterogeneity in hepatocellular carcinoma: imaging-pathologic correlation.
A. Dong (2014)
Evan R. Delgado (2014)
Inter- and Intratumor Heterogeneity in Hepatocellular Carcinoma
E. Denisov (2016)
GSK-3 phosphorylation and alteration of -catenin in hepatocellular carcinoma
K. Ban (2003)
Genomic and Epigenomic Heterogeneity of Hepatocellular Carcinoma.
Dechen Lin (2017)
Selective Retention of an Inactive Allele of the DKK2 Tumor Suppressor Gene in Hepatocellular Carcinoma
Yung-Feng Lin (2016)
High levels of p53 protein expression do not correlate with p53 mutations in hepatocellular carcinoma
M. Anzola (2004)
Advances in molecular classification and precision oncology in hepatocellular carcinoma.
Sandra Rebouissou (2020)
See more
Semantic Scholar Logo Some data provided by SemanticScholar