Beta-catenin expression in hepatocellular carcinoma: a possible participation of beta-catenin in the dedifferentiation process.
BACKGROUND
beta-Catenin is known as a multifunctional protein acting as a regulator of the cadherin-mediated cell-cell adhesion system and in the Wingless/Wnt signal transduction pathway. Recent studies reported mutation of the beta-catenin gene in some tissues of hepatocellular carcinoma (HCC).


METHODS
'Nodule-in-nodule' appearance is a feature of well-differentiated HCC containing a distinct nodule of less-differentiated cancer tissue inside, and it is presumed to be a morphological expression of the dedifferentiation process. The present study immunohistochemically investigated the beta-catenin expression according to the dedifferentiation process of HCC, that is, in small well-differentiated HCC with indistinct margins, HCC with a 'nodule-in-nodule' appearance, moderately differentiated HCC, which does not have a 'nodule-in-nodule' appearance, and sarcomatous HCC.


RESULTS
The expression of beta-catenin was observed in approximately 70% of small well-differentiated HCC with indistinct margins. In HCC with a 'nodule-in-nodule' appearance, membranous expression of beta-catenin was higher in the well-differentiated cancer tissues than in the less-differentiated cancer tissues (P < 0.01), cytoplasmic expression was higher in the less-differentiated cancer tissues (P < 0.01), and nuclear expression was higher in the less-differentiated cancer tissues (P < 0.001). In moderately differentiated HCC, tumors with membranous expression of beta-catenin had more frequent intrahepatic metastasis than those without having the expression (P < 0.001).


CONCLUSIONS
Accumulation of beta-catenin was already present in the early stage of HCC, and in less-differentiated cancer tissue the membranous expression of beta-catenin could be related to intrahepatic metastasis.
Suzuki
Tetsuya
T
Department of Pathology, Kurume University School of Medicine, Fukuoka, Japan. tetsuyasuzuki@mac.com
Yano
Hirohisa
H
Nakashima
Yutaka
Y
Nakashima
Osamu
O
Kojiro
Masamichi
M
D000368:Aged; D015820:Cadherins / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015534:Trans-Activators / Q000096:biosynthesis*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D019394:Ki-67 Antigen; D015534:Trans-Activators; D051176:beta Catenin