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Twisted gastrulation expression in cholangiocellular and hepatocellular carcinoma
  1. Jolene Johnston1,
  2. Redha Al-Bahrani1,
  3. Yasser Abuetabh1,
  4. Brian Chiu1,
  5. Cynthia L Forsman2,3,
  6. Seishi Nagamori4,
  7. Roger Leng1,
  8. Anna Petryk2,3,
  9. Consolato Sergi1,5
  1. 1Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, Alberta, Canada
  2. 2Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
  3. 3Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA
  4. 4Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
  5. 5Institute of Pathology, Medical University of Innsbruck, Innsbruck, Tyrol, Austria
  1. Correspondence to Dr Consolato Sergi, Department of Laboratory Medicine and Pathology, University of Alberta Hospital, 8440 112 Street, NW, Edmonton, AB T6G 2B7, Canada; sergi{at}


Aims 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.

  • Cancer
  • cancer genetics
  • carcinoma
  • breast
  • liver
  • bone
  • endocrinology
  • growth
  • placenta
  • histopathology
  • apoptosis
  • morbid anatomy

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  • JJ and RA-B contributed equally to this work.

  • Competing interests None.

  • Ethics approval This study was approved by the institutional Human Research Ethics Board (University of Alberta, Edmonton, Canada; HREB approval #20274) and operationally by the provincial Health Care Provider (Alberta Health Services).

  • Provenance and peer review Not commissioned; externally peer reviewed.