Z Gastroenterol 2011; 49 - P2_61
DOI: 10.1055/s-0030-1269578

Delta like ligand 4 expression in the endothelium of hepatocellular carcinoma is associated with poor tumor differentiation and early tumor stages

C Mogler 1, H Weng 2, S Singer 3, P Schirmacher 4, T Longerich 4
  • 1Department of Pathology, University of Heidelberg, Heidelberg
  • 2Medizinische Fakultät Mannheim der Universität Heidelberg, II. Medizinische Klinik, Mannheim, Deutschland
  • 3Department of Clinical Pathology, University of Heidelberg, Heidelberg
  • 4Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg

Aims: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Most tumors are stroma-poor but highly vascularised. Overexpression of the tip cell marker and Notch ligand delta like ligand 4 (DLL4) has been described in many tumor entities but not yet investigated in human HCCs. First attempts have been made to further characterize tumor vasculature, but to date no clear data exist about sprouting angiogenesis and its relation to malignant transformation in HCCs (“angiogenic switch“).

Methods: Tissue micorarrays (TMAs) including overall 192 HCCs, 9 Dysplastic nodules (DN) and 12 normal liver samples (NL) were investigated for DLL4 expression and vessel marker CD34 for microvessel density (MVD) and correlated with clinical data.

Results: DLL4 expression was not present in NL or DN but in 22 HCCs (12.72%), distributed in 2 different expression patterns: a “single cells positive“ pattern, where only few (<10) endothelial cells appeared to be positive and a more diffuse pattern with multiple positive endothelial cells. Diffuse expression pattern could be associated with poor tumor differentiation (p<0.05) and early tumor stages (p=0.058) but not etiology (p>0.05). Single cell positive pattern had significant lower MVD compared to DLL4 negative HCC and a clear association with advanced tumor stages compared to the diffuse expression pattern (p<0.05).

Conclusion: Compared to pre-existing DLL4 expression data from other types of carcinomas (colon, breast), DLL4 expression in HCC is less frequent but not a neglectable event. Both detected DLL4 expression patterns could be associated with varying conditions. Our data therefore suggest that DLL4 expression and especially changes in its expression profile might play a role in the angiogenic switch. Further investigations in vitro an in vivo are needed to better understand the role of DLL4 in HCC progression.

DLL4 - HCC - angiogenesis