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10.1245/ASO.2003.08.924
Annals of Surgical Oncology 10:1123 (2003)
© 2003 Society of Surgical Oncology
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LETTER TO THE EDITOR

Prognostic Value of Plasma and Serum VEGF Levels in Patients With Resectable Hepatocellular Carcinoma

Simone Ferrero, MD and Nicola Ragni, MD

Department of Obstetrics and Gynaecology, San Martino Hospital, University of Genoa, Largo R. Benzi 1, Genoa, Italy

To the Editor:

We read with interest the article titled "Prognostic Significance of Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor, and Angiogenin in Patients With Resectable Hepatocellular Carcinoma After Surgery".1 We would like to bring your attention to some methodological concerns that have arisen.

The authors measured serum vascular endothelial growth factor (VEGF) levels. The serum VEGF concentration changes depending on clotting duration.2,3 The interval between sample collection and processing is relevant; it should be standardized and declared. Hormbrey et al. proved that there is no significant difference in VEGF levels in serum samples processed between 30 and 60 minutes after collection, but the difference becomes significant when the samples are processed after 2–6 hours.3 In a clinical situation, where blood samples are taken and left for variable times before processing, the contribution from the clotting process may interfere with the measurement of circulating VEGF levels at the time of sampling. Moreover, even if a strict uniformity of clotting time could be applied to all samples, the interpersonal variation in generation of VEGF in clotted samples may make the interpretation of the measurement very difficult.

The authors reported a positive correlation between serum VEGF level and the platelet count. This confirms the results of previous studies suggesting that the serum measurement of VEGF reflects the clotting process rather than VEGF synthesis by peripheral tissues.2,4,5 Despite recent evidence supporting the use of serum VEGF level and an indirect estimate of tumor VEGF expression,6 we believe that it would be interesting to evaluate the prognostic value of plasma VEGF in patients with hepatocellular carcinoma. In plasma, platelet degranulation is minimized by adding anticoagulants to the blood samples, and as a consequence, plasma VEGF concentrations are up to 20 times lower than the matched serum VEGF concentrations.5 When utilizing plasma for VEGF measurement, the interval between sample collection and processing is not as critical as in the case of serum, and the normalization of VEGF levels by platelet count is not necessary. In light of these considerations, we believe that the measurement of circulating plasma VEGF may improve the predictive value of the test.

REFERENCES

  1. Chao Y, Li CP, Chau GY, et al. Prognostic significance of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin in patients with resectable hepatocellular carcinoma after surgery. Ann Surg Oncol 2003; 10: 355–62.[Abstract/Free Full Text]
  2. Webb NJ, Bottomley MJ, Watson CJ, Brenchley PE. Vascular endothelial growth factor (VEGF) is released from platelets during blood clotting: implications for measurement of circulating VEGF levels in clinical disease. Clin Sci 1998; 94: 395–404.[Medline]
  3. Hormbrey E, Gillespie P, Turner K, et al. A critical review of vascular endothelial growth factor (VEGF) analysis in peripheral blood: is the current literature meaningful? Clin Exp Metastasis 2002; 19: 651–63.[CrossRef][Medline]
  4. Verheul HM, Hoekman K, Luykx-de Bakker S, et al. Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 1997; 3: 2187–90.[Abstract/Free Full Text]
  5. Banks RE, Forbes MA, Kinsey SE, et al. Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer 1998; 77: 956–64.[Medline]
  6. Poon RT, Lau CP, Cheung ST, Yu WC, Fan ST. Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma. Cancer Res 2003; 63: 3121–6.[Abstract/Free Full Text]




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