Open Access Research article

Clinical procedure for colon carcinoma tissue sampling directly affects the cancer marker-capacity of VEGF family members

Sarah Pringels1, Nancy Van Damme2, Bram De Craene13, Piet Pattyn2, Wim Ceelen2, Marc Peeters4 and Johan Grooten1*

Author affiliations

1 Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde, 9052, Belgium

2 Department of Surgery, Ghent University Hospital, De Pintelaan 185, Gent, 9000, Belgium

3 Department for Molecular Biomedical Research VIB, Zwijnaarde, 9052, Belgium

4 Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, Edegem, 2650, Belgium

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Citation and License

BMC Cancer 2012, 12:515  doi:10.1186/1471-2407-12-515

Published: 13 November 2012



mRNA levels of members of the Vascular Endothelial Growth Factor family (VEGF-A, -B, -C, -D, Placental Growth Factor/PlGF) have been investigated as tissue-based markers of colon cancer. These studies, which used specimens obtained by surgical resection or colonoscopic biopsy, yielded contradictory results. We studied the effect of the sampling method on the marker accuracy of VEGF family members.


Comparative RT-qPCR analysis was performed on healthy colon and colon carcinoma samples obtained by biopsy (nā€‰=ā€‰38) or resection (nā€‰=ā€‰39) to measure mRNA expression levels of individual VEGF family members. mRNA levels of genes encoding the eicosanoid enzymes cyclooxygenase 2 (COX2) and 5-lipoxygenase (5-LOX) and of genes encoding the hypoxia markers glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX) were included as markers for cellular stress and hypoxia.


Expression levels of COX2, 5-LOX, GLUT-1 and CAIX revealed the occurrence in healthy colon resection samples of hypoxic cellular stress and a concurrent increment of basal expression levels of VEGF family members. This increment abolished differential expression of VEGF-B and VEGF-C in matched carcinoma resection samples and created a surgery-induced underexpression of VEGF-D. VEGF-A and PlGF showed strong overexpression in carcinoma samples regardless of the sampling method.


Sampling-induced hypoxia in resection samples but not in biopsy samples affects the marker-reliability of VEGF family members. Therefore, biopsy samples provide a more accurate report on VEGF family mRNA levels. Furthermore, this limited expression analysis proposes VEGF-A and PlGF as reliable, sampling procedure insensitive mRNA-markers for molecular diagnosis of colon cancer.

VEGF family members; Colon cancer; Sampling procedure; Biomarker; Hypoxic stress