Z Gastroenterol 2009; 47 - P043
DOI: 10.1055/s-0029-1241294

CXCR4– a new antiangiogenic target in colorectal carcinoma?

B Ingold 1, S Schulz 2, J Budczies 1, U Neumann 3, MPA Ebert 4, W Weichert 1, C Röcken 1
  • 1Institut für Pathologie, CCM, Charité – Universitätsmedizin, Berlin, Germany
  • 2Institut für Pharmakologie und Toxikologie, Friedrich Schiller Universität, Jena, Germany
  • 3Klinik für Allgemein- Viszeral- und Transplantationschirurgie Charité – Universitätsmedizin, Berlin, Germany
  • 4II Medizinische Klinik des Klinikums rechts der Isar, Technische Universität München, München, Germany

Introduction: The chemokine receptor CXCR4 plays a prominent role in the tumour biology of many different tumour entities, promoting angiogenesis and migration of tumour cells to metastatic sites. The impact of CXCR4 expression for tumour biology has been described in various gastrointestinal malignancies, but data on in situ expression and clinico-pathological correlations are sparse.

Aims: In the present study, we filled this gap of information and evaluated CXCR4 expression in colorectal carcinoma. We correlated the CXCR4 immunoreactivity with the expression of the CXCR4 ligand CXCL12 and an ample set of clinico-pathological data, including patient survival.

Methods: Immunohistological profiles were assessed by using a novel specific rabbit anti-CXCR4 antibody and a commercially available CXCL12 antibody on tissue microarrays generated from 402 colorectal carcinomas.

Results: CXCR4 expressing tumour cells were observed in 31% of the cases, expression correlated only with venous blood vessel invasion (p=0.049). In addition, CXCR4 was found in tumour-microvessels in 25% of CRCs. This pattern of CXCR4 expression correlated significantly with T- (p=0.008), N- (p=0.009), M- (p=0.043), L- (p=0.014), and V-category (p=0.043) as well as with International Union Against Cancer (UICC)-stage (p=0.001). Furthermore, in nodal negative CRCs, vascular CXCR4 expression was an independent adverse prognostic factor [HR 2.87 (1.31–6.29), p=0.009]. No correlation was found with CXCL12 expression.

Conclusions: Our data provide evidence that CXCR4 plays an important role in tumour angiogenesis of CRC. Therefore the CXCR4 pathway is a promising therapeutic target for antiangiogenic therapies in CRC.