Twisted gastrulation expression in cholangiocellular and hepatocellular carcinoma.
OBJECTIVE
To assess the expression of Twisted gastrulation (TWSG1) protein, which regulates the activity of bone morphogenetic proteins (BMPs) in the extracellular space in malignant epithelial tumours of the liver.


METHODS
Thirteen hepatocellular carcinoma (HCC) samples and 12 intrahepatic cholangiocellular carcinoma (CCA) samples were compiled into diagnosis-specific tissue microarrays. Sections were immunostained with a monoclonal antibody against TWSG1 and a polyclonal antibody against BMP4. Human cell lines were also used, including one HCC cell line (HepG2), three CCA cell lines (OZ, Huh-28, HuCCT-1) and a Papova-immortalised normal hepatocyte cell line (THLE-3) for western blot analysis (WBA).


RESULTS
Immunostaining and WBA showed a stronger TWSG1 expression in CCA than in HCC. The difference in expression was significant (p<0.05), and the immunohistochemical signal was particularly evident in the malignant epithelial areas close to desmoplastic stroma in CCA and in the areas of glandular differentiation in HCC. No expression was seen in normal hepatocytes. Interestingly, BMP4 was fully expressed in CCA and only partly in HCC. WBA showed a band for BMP4 in both CCA and HCC cell lines.


CONCLUSIONS
TWSG1 is expressed in both malignant epithelial carcinomas, although the level of expression is higher in CCA than in HCC and seems to correlate at least partially with BMP4 expression.
Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, Alberta, Canada.
Jolene
J
Johnston
Redha
R
Al-Bahrani
Yasser
Y
Abuetabh
Brian
B
Chiu
Cynthia L
CL
Forsman
Seishi
S
Nagamori
Roger
R
Leng
Anna
A
Petryk
Consolato
C
Sergi
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis
D055415:Bone Morphogenetic Protein 4; D009363:Neoplasm Proteins; D011506:Proteins; C576635:TWSG1 protein, human