PMID- 10487827
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20190607
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 155
IP  - 3
DP  - 1999 Sep
TI  - Nuclear accumulation of mutated beta-catenin in hepatocellular carcinoma is
      associated with increased cell proliferation.
PG  - 703-10
AB  - Inappropriate activation of the Wnt pathway resulting from beta-catenin gene
      alterations has recently been implicated in the development of hepatocellular
      carcinoma (HCC). To explore the in vivo effects of mutated beta-catenin, HCC
      specimens from 32 patients carrying one or several tumors were screened for
      somatic mutations in exon 3 of the beta-catenin gene, and the expression and
      subcellular localization of beta-catenin was studied by immunohistochemistry.
      Missense mutations or interstitial deletions in beta-catenin exon 3 were detected
      in 12 of 35 (34%) HCC samples. After immunostaining, most tumors exhibited
      increased membranous and/or cytoplasmic expression of beta-catenin compared with 
      adjacent nontumoral liver. Strong nuclear accumulation of beta-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 beta-catenin was significantly associated with the presence
      of mutations in the beta-catenin gene (P < 0.005). Moreover, nuclear beta-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/beta-catenin
      pathway in HCC results mainly from somatic mutations in the beta-catenin gene and
      may promote tumor progression by stimulating tumor cell proliferation.
FAU - Nhieu, J T
AU  - Nhieu JT
AD  - Departement de Pathologie, Service de Chirurgie, Hopital Henri Mondor - AP-HP,
      Creteil, Paris, France.
FAU - Renard, C A
AU  - Renard CA
FAU - Wei, Y
AU  - Wei Y
FAU - Cherqui, D
AU  - Cherqui D
FAU - Zafrani, E S
AU  - Zafrani ES
FAU - Buendia, M A
AU  - Buendia MA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
SB  - AIM
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence
MH  - Carcinoma, Hepatocellular/*metabolism/mortality/pathology
MH  - Cell Division/genetics
MH  - Cell Nucleus/*metabolism
MH  - Cytoskeletal Proteins/*biosynthesis/*genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Ki-67 Antigen/metabolism
MH  - Liver Neoplasms/*metabolism/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Mitotic Index
MH  - Mutation
MH  - Polymerase Chain Reaction
MH  - Recurrence
MH  - Survival Rate
MH  - *Trans-Activators
MH  - beta Catenin
PMC - PMC1866892
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - S0002-9440(10)65168-1 [pii]
AID - 10.1016/s0002-9440(10)65168-1 [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Sep;155(3):703-10. doi: 10.1016/s0002-9440(10)65168-1.