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125. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

22. - 25.04.2008, Berlin

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Intrinsic Angiostatic Immune Reaction in Colorectal Carcinoma: Implications for Patient´s Survival and Antiangiogenic Therapy

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  • E. Naschberger - Chirurgische Klinik, Universitätsklinikum Erlangen, Erlangen, Deutschland
  • R.S. Croner - Chirurgische Klinik, Universitätsklinikum Erlangen, Erlangen, Deutschland
  • S. Merkel - Chirurgische Klinik, Universitätsklinikum Erlangen, Erlangen, Deutschland
  • P. Tripal - Chirurgische Klinik, Universitätsklinikum Erlangen, Erlangen, Deutschland
  • W.M. Brueckl - Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
  • T. Papadopoulos - Institut für Pathologie, Universitätsklinikum Erlangen, Erlangen, Deutschland
  • W. Hohenberger - Chirurgische Klinik, Universitätsklinikum Erlangen, Erlangen, Deutschland
  • corresponding author M. Stürzl - Chirurgische Klinik, Universitätsklinikum Erlangen, Erlangen, Deutschland

Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. Doc08dgch9188

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgch2008/08dgch020.shtml

Published: April 16, 2008

© 2008 Naschberger et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: Angiogenesis and inflammation are the two major stroma reactions in colorectal carcinoma (CRC). Guanylate binding protein-1 (GBP-1) is a key mediator of inflammation-associated angiostasis. Therefore, we hypothesized that GBP-1 expression may indicate intrinsic angiostasis and may be associated with an improved outcome in CRC patients.

Materials and methods: Affymetrix microarray analyses, RT-PCR, multiplex RT-PCR for simultaneous detection of GBP-1, CXCL9, CXCL10, CXCL11, immunohistochemical detection of GBP-1 in CRC tissue arrays.

Results: GBP-1 was strongly expressed in endothelial cells and immune cells in the desmoplastic stroma of 32% of CRC as determined by immunohistochemical investigation of 388 sporadic CRC. Cancer-related 5-year survival was highly significant (p<0.001) increased (16.2%) in patients with GBP-1-positive CRC. Multivariate analysis showed that GBP-1 is an independent prognostic factor indicating a reduction of the relative risk of cancer-related death by the half (p=0.032). A comparative transcriptome analysis (22,215 probe sets) of GBP-1-positive (n=12) and –negative (n=12) tumors showed that particularly IFN-γ-induced genes including the major antiangiogenic chemokines CXCL9, CXCL10 and CXCL11 were coexpressed with GBP-1.

Conclusion: Our results indicated that GBP-1 is a novel biomarker and an active component of a Th-1-like angiostatic immune reaction (IAR). IAR in CRC is beneficial for the patient´s cancer-related survival and the identification of tumors with IAR may provide a novel criterion for patient selection to improve response rates to antiangiogenic therapy. Induction of IAR may be a promising approach for the clinical treatment of CRC.