VEGFR1: Target for Anti-Angiogenic Therapy? An Immunohistochemical Study Highlighting Heterogeneity of Tumor-Associated Endothelial Cells
Nicky D'Haene, Francoise Hulet, Justine Allard, Calliope Maris, Christine Decaestecker, Isabelle Salmon. Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium; Center for Microscopy and Molecular Imaging, ULB, Gosselies, Belgium
Background: Research on tumour angiogenesis has mainly focused on vascular endothelial growth factor (VEGF) family and methods to block its actions. The fact that VEGFR1 could promote angiogenesis in pathological conditions makes it an attractive potential target. However, reports on the VEGFR1 expression in tumor-associated endothelial cells (EC) are limited. We decided to evaluate VEGFR1 expression in EC of human tissues.
Design: Immunohistochemical EC VEGFR1 expression was submitted to quantitative (computer-assisted microscopy) evaluation in a retrospective series of 130 normal and 785 malignant tumor tissues (including oral mucosa, esophagus, stomach, colon, thyroid, prostate and CNS). Results were related to clinical variables for colorectal carcinomas (CRC), glioblastomas (GBM) and thyroid carcinomas. EC VEGFR1 expression was also evaluated in a prospective series of 40 matched normal and tumor tissues (including lung, stomach, colon, liver and kidney).
Results: The data show that in normal tissue, EC expression of VEGFR1 was low. In contrast, a statistically significant increase of VEGFR1 expression was observed in EC of tumor tissues (Mann-Withney test: p=0.006 – Wilcoxon test for matched cases p<10-6). However, a great heterogeneity was observed depending of tumor. The highest increases were observed for EC of oral squamous cell carcinomas and papillary thyroid carcinomas as compared to the normal counterpart (p=0.009 and p=0.002 respectively). For pT1-4N0-2M0-staged CRC (n=269), higher EC VEGFR1 expression was an independent prognostic factor in terms of metachronous metastasis (p=0.03). Altough the highest EC expressions of VEGFR1 was observed for some cases of GBM, EC VEGFR1 expression in GBM (n=181) was not associated with any prognostic values. Regarding thyroid carcinomas (n=42), higher EC VEGFR1 expression seems to be associated with lymph node metastasis (p=0.08), however this trend should be confirmed in a larger series.
Conclusions: This work illustrates the importance of studying target distribution. By its specific expression by tumor-associated EC VEGFR1 could be an interesting therapeutic target. However, expression heterogeneity across tumor types should be taken into account. Interestingly, higher EC VEGFR1 expression appears as being involved in CRC progression, suggesting that targeting EC VEGFR1 could offer novel opportunities for CRC treatment.
Monday, March 4, 2013 1:00 PM
Poster Session II # 271, Monday Afternoon