Virchows Archiv

, Volume 458, Issue 6, pp 697–708 | Cite as

The homeobox gene HLXB9 is upregulated in a morphological subset of poorly differentiated hepatocellular carcinoma

  • Ludwig WilkensEmail author
  • Rolf Jaggi
  • Caroline Hammer
  • Daniel Inderbitzin
  • Olivier Giger
  • Nils von Neuhoff
Original Article


The prognostic outcome for hepatocellular carcinoma (HCC) remains poor. Disease progression is accompanied by dedifferentiation of the carcinoma, a process that is not well understood. The aim of this study was to get more insight into the molecular characteristics of dedifferentiated carcinomas using high throughput techniques. Microarray-based global gene expression analysis was performed on five poorly differentiated HCC cell lines compared with non-neoplastic hepatic controls and a set of three cholangiolar carcinoma (CC) cell lines. The gene with the highest upregulation was HLXB9. HLXB9 is a gene of the homeobox genfamily important for the development of the pancreas. RT-PCR confirmed the upregulation of HLXB9 in surgical specimens of carcinoma tissue, suggesting its biological significance. Interestingly, HLXB9 upregulation was primary observed in poorly differentiated HCC with a pseudoglandular pattern compared with a solid pattern HCC or in moderate or well-differentiated HCC. Additional the expression of translated HLXB9, the protein HB9 (NCBI: NP_001158727), was analyzed by western blotting. Expression of HB9 was only detected in the cytoplasm but not in the nuclei of the HCC cells. For validation CC were also investigated. Again, we found an upregulation of HLXB9 in CC cells accompanied by an expression of HB9 in the cytoplasms of these tumor cells, respectively. In conclusion, homeobox HLXB9 is upregulated in poorly differentiated HCC with a pseudoglandular pattern. The translated HB9 protein is found in the cytoplasm of these HCC and CC. We therefore assume HLXB9 as a possible link in the understanding of the development of HCC and CC, respectively.


Hepatocellular carcinoma Cholangiocellular carcinoma HLXB9 Histological differentiation 


Conflict of interest

The authors declare that they have no conflict of interests.


This work was supported by the Schweizerischer Nationalfonds (SNF, grant 31003A-118065).


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ludwig Wilkens
    • 1
    • 2
    Email author
  • Rolf Jaggi
    • 3
  • Caroline Hammer
    • 1
  • Daniel Inderbitzin
    • 4
  • Olivier Giger
    • 1
  • Nils von Neuhoff
    • 5
  1. 1.Institute of PathologyUniversity of BernBernSwitzerland
  2. 2.Institute of PathologyHospitals of the Region HannoverHannoverGermany
  3. 3.Department of Clinical ResearchUniversity of BernBernSwitzerland
  4. 4.Department of Visceral and Transplantation SurgeryInselspital BernBernSwitzerland
  5. 5.Institute of Cell and Molecular PathologyMedical School HannoverHannoverGermany

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