Abstract 3419: VEGFA and SLC2A1 are prognostic biomarkers for patients with resectable colorectal cancer liver metastases
Authors: Goos Jeroen A.C.M. , de Cuba Erienne M.V. , Coupe Veerle M.H. , Diosdado Begona , Delis-van Diemen Pien M. , Karga Cemile , Belien Jeroen A.M. , Menke - Van der Houven van Oordt C. Willemien , Geldof Albert A. , Meijer Gerrit A. , Hoekstra Otto S. , Fijneman Remond J. A. 
Published: August 2015

Background: Colorectal cancer (CRC) is the second leading cause of cancer mortality in developed countries, which is mainly due to hematogenous dissemination to the liver. Resection of CRC liver metastases (CRCLM) is the only treatment option with curative intent. Patient eligibility relies on standard prognostic clinicopathological variables, however, 5-year survival rates hardly exceed 40% indicating the need for better prognostic biomarkers to improve clinical management of CRCLM patients. Overexpression of hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (SLC2A1; also known as GLUT1) and vascular endothelial growth factor A (VEGFA) have been associated with tumor progression and poor prognosis of CRC patients.

Aim: To investigate the individual and combined prognostic value of HIF1α, SLC2A1 and VEGFA in a multi-institutional cohort of patients with resected colorectal cancer liver metastasis (CRCLM).

Methods: Tissue microarrays were generated using CRCLM and patient-matched primary CRC from patients who underwent CRCLM resection between 1990 and 2010. Prognostic value of HIF1α, SLC2A1 and VEGFA was determined by immunohistochemistry. A 500-fold cross-validated hazard rate ratio (HRRav) for overall survival was calculated.

Results: Protein expression of HIF1α, SLC2A1 and VEGFA could be evaluated in 328, 350 and 335 patients, respectively. HIF1α expression was not associated with survival. High SLC2A1 expression was associated with good prognosis (HRRav0.67; P(HRR&gt;1)&lt;.01) and high VEGFA expression to poor prognosis (HRRav1.84; P(HRR&lt;1) = .02), also after multivariate analysis including established clinicopathological prognostic variables (HRRav0.67; P(HRR&gt;1)&lt;.01 and HRRav1.50; P(HRR&lt;1) = .02, respectively). SLC2A1 showed prognostic value in patients who were treated with systemic therapy (P&lt;.01), while the prognostic value of VEGFA expression was mainly observed in patients who were not treated with systemic therapy (P&lt;.01). Poorest prognosis was observed in patients with both low SLC2A1 and high VEGFA expression (P&lt;.01).

Conclusions: VEGFA and SLC2A1 expression are prognostic molecular biomarkers for CRCLM patients with added value to established clinicopathological variables. VEGFA is a key molecular target for anti-angiogenesis therapy in metastatic CRC patients, and SLC2A1 increases the uptake of glucose which is visualized by 18FDG-PET imaging. Therefore, these biomarkers provide opportunities to improve clinical management of CRCLM patients.

Citation Format: Jeroen A.C.M. Goos, Erienne M.V. de Cuba, Veerle M.H. Coupe, Begona Diosdado, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Belien, C. Willemien Menke - Van der Houven van Oordt, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J. A. Fijneman, on behalf of the DeCoDe PET group. VEGFA and SLC2A1 are prognostic biomarkers for patients with resectable colorectal cancer liver metastases. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3419. doi:10.1158/1538-7445.AM2015-3419