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Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA) Predict Survival After Resection of Colorectal Cancer Liver Metastasis

Goos, Jeroen A. C. M. MSc*,†; de Cuba, Erienne M. V. MD*; Coupé, Veerle M. H. PhD; Diosdado, Begoña PhD*; Delis-Van Diemen, Pien M. BSc*; Karga, Cemile MSc; Beliën, Jeroen A. M. PhD*; Oordt, C. Willemien Menke-Van der Houven van PhD, MD§; Geldof, Albert A. PhD; Meijer, Gerrit A. PhD, MD*; Hoekstra, Otto S. PhD, MD; Fijneman, Remond J. A. PhD*on behalf of the DeCoDe PET Group

doi: 10.1097/SLA.0000000000001109

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

Background: In the majority of patients with CRCLM, resection seems not to be curative, despite its curative intent. Overexpression of hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (SLC2A1; also known as GLUT1), and VEGFA has been associated with tumor progression and poor prognosis of patients with colorectal cancer (CRC).

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: HIF1α, SLC2A1, and VEGFA expression could be evaluated in 328, 350, and 335 patients, respectively. High SLC2A1 expression was associated with good prognosis (HRRav, 0.67; P (HRR >1) < 0.01) and high VEGFA expression to poor prognosis (HRRav, 1.84; P (HRR < 1) = 0.02), also after multivariate analysis including established clinicopathological prognostic variables (HRRav, 0.67; P (HRR > 1) < 0.01 and HRRav, 1.50; P (HRR <1) = 0.02, respectively). SLC2A1 showed prognostic value particularly in patients treated with systemic therapy (P < 0.01), whereas the prognostic value of VEGFA expression was mainly observed in patients not treated with systemic therapy (P < 0.01). Prognosis was especially poor in patients with both low SLC2A1 and high VEGFA expression (P < 0.01). HIF1α expression was not associated with survival.

Conclusions: SLC2A1 and VEGFA expression are prognostic molecular biomarkers for patients with CRCLM with added value to established clinicopathological variables.

Supplemental Digital Content is available in the text

*Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

§Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.

Reprints: Remond J. A. Fijneman, PhD, Department of Pathology (Tumor Profiling Unit), VU University Medical Center, CCA 1.08, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. E-mail:

Collaborators of the DeCoDe PET group are in alphabetical order per medical center: N.C.T. van Grieken, L.R. Perk, M.P. van den Tol, E.A. te Velde, A.D. Windhorst (VU University/VU University Medical Center—Amsterdam); J. Baas, A.M. Rijken (Amphia Medical Center—Breda); M.W. van Beek, H.J. Pijpers (Catharina Medical Center/PAMM Foundation—Eindhoven); H. Bril, H.B.A.C. Stockmann, A. Zwijnenburg (Kennemer Gasthuis/Spaarne Medical Center—Haarlem); K. Bosscha, A.J. van den Brule, C.J. Hoekstra, J.C. van der Linden (Jeroen Bosch Medical Center—Hertogenbosch); I.H. Borel Rinkes, P.J. van Diest, R. van Hillegersberg, O. Kranenburg, M.G. Lam, N. Snoeren (UMCU—Utrecht); I.H. Liem, R.M. Roumen, W. Vening (MMC—Veldhoven).

Disclosure: Supported by the Center for Translational Molecular Medicine, DeCoDe project (grant 03O-101) funds. The authors declare no conflicts of interest.

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