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Quantitative Correlation of Serum Levels and Tumor Expression of Vascular Endothelial Growth Factor in Patients with Hepatocellular Carcinoma

Centre for the Study of Liver Disease and Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China

Recent studies have suggested that serum levels of vascular endothelial growth factor (VEGF) may provide useful prognostic information in patients with various types of cancers. However, there has been a debate on whether serum VEGF level is a true reflection of tumor angiogenic activity in cancer patients. This debate originates from the finding that most VEGF in the serum is released from platelets during clotting. It has been postulated that platelet may serve the role of storage for circulating VEGF derived from the tumors. We conducted a study to clarify whether the platelet load of VEGF in the circulation correlates with tumor expression of VEGF. We measured quantitatively the serum VEGF₁₆₅ levels and tumor cytosolic VEGF₁₆₅ concentration by an ELISA and tumor VEGF₁₆₅ mRNA by real-time quantitative reverse transcription-PCR in 60 patients with hepatocellular carcinoma. Serum VEGF₁₆₅ levels correlated significantly with platelet counts (r = 0.662, P < 0.001). When corrected for platelet count, serum VEGF₁₆₅/platelet correlated significantly with tumor cytosolic VEGF₁₆₅ concentration (r = 0.447, P = 0.006), which in turn correlated with VEGF₁₆₅ mRNA expression in the tumors (r = 0.315, P = 0.020). Advancing tumor stage was associated with a significant increase in tumor cytosolic VEGF₁₆₅ concentration (P = 0.006), tumor VEGF₁₆₅ mRNA expression (P = 0.012), serum VEGF₁₆₅/platelet (P = 0.001), and serum VEGF₁₆₅ levels (P = 0.003). In conclusion, our data showed that the platelet load of VEGF in the circulation correlated positively with tumor VEGF expression. This study provides strong evidence that supports the use of serum VEGF level as an indirect estimate of tumor VEGF expression.

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