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Int. J. Mol. Sci. 2018, 19(11), 3536; https://doi.org/10.3390/ijms19113536

The Prognostic Value of the Combination of Low VEGFR-1 and High VEGFR-2 Expression in Endothelial Cells of Colorectal Cancer

1
Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB),1070 Brussels, Belgium
2
DIAPath—Center for Microscopy and Molecular Imaging, ULB, 6041 Gosselies, Belgium
3
Laboratory of Image, Signal Processing and Acoustics, Ecole Polytechnique de Bruxelles, ULB, 1050 Brussels, Belgium
4
CMP-Cerba European Labs, 1070 Brussels, Belgium
Current address: Laboratory of Pathology, Erasme University Hospital, 808 Route de Lennik, 1070 Brussels, Belgium
*
Author to whom correspondence should be addressed.
Received: 10 August 2018 / Revised: 17 October 2018 / Accepted: 31 October 2018 / Published: 9 November 2018
(This article belongs to the Special Issue Basic and Translational Research in Colorectal Cancer)
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Abstract

Research on tumor angiogenesis has mainly focused on the vascular endothelial growth factor (VEGF) family and on methods to block its actions. However, reports on VEGF receptor (VEGFR) expression in tumor-associated endothelial cells (ECs) are limited. Thus, we evaluated VEGF, VEGFR-1 and VEGFR-2 expression in ECs of colorectal cancer (CRC) using immunohistochemistry. VEGF, VEGFR-1 and -2 expression in ECs was quantitatively evaluated by digital image analysis in a retrospective series of 204 tumor tissue samples and related to clinical variables. The data show that the VEGF, VEGFR-1 and VEGFR-2 expression in ECs is heterogeneous. Multivariate analysis including a set of clinicopathological variables reveals that high EC VEGFR-1 expression is an independent prognostic factor for overall survival (OS). The combination of low VEGFR-1 and high VEGFR-2 expression in ECs outperforms models integrating VEGFR-1 and VEGFR-2 as separate markers. Indeed, this VEGFR-1_VEGFR-2 combination is an independent negative prognostic factor for OS (p = 0.012) and metastasis-free survival (p = 0.007). In conclusion, this work illustrates the importance of studying the distribution of VEGF members in ECs of CRC. Interestingly, our preliminary data suggest that high VEGFR-1 and low VEGFR-2 expression in ECs appear to be involved in the progression of CRC, suggesting that targeting EC VEGFR-1 could offer novel opportunities for CRC treatment. However, a prospective validation study is needed. View Full-Text
Keywords: VEGFR-1; VEGFR-2; endothelial cells; colorectal cancer; prognosis VEGFR-1; VEGFR-2; endothelial cells; colorectal cancer; prognosis
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D’Haene, N.; Koopmansch, C.; Van Eycke, Y.-R.; Hulet, F.; Allard, J.; Bouri, S.; Rorive, S.; Remmelink, M.; Decaestecker, C.; Maris, C.; Salmon, I. The Prognostic Value of the Combination of Low VEGFR-1 and High VEGFR-2 Expression in Endothelial Cells of Colorectal Cancer. Int. J. Mol. Sci. 2018, 19, 3536.

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