Vascular Endothelial Growth Factor (VEGF), Serum

Assessment of tumor progression and prognosis.

Results of this test are labeled for research purposes only by the assay's manufacturer. The performance characteristics of this assay have not been established by the manufacturer. The result should not be used for treatment or for diagnostic purposes without confirmation of the diagnosis by another medically established diagnostic product or procedure. The performance characteristics were determined by LabCorp.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a homodimeric 34 to 45 kilodalton, heparin-binding glycoprotein. VEGF has potent angiogenic, mitogenic, and vascular permeability-enhancing activities specific for endothelial cells.¹ VEGF is thought to play an important role in several physiologic processes, including wound healing, ovulation, menstruation, maintenance of blood pressure, and pregnancy.¹ VEGF has also been associated with a number of pathologic processes that involve angiogenesis, including arthritis, psoriasis, macular degeneration, and diabetic retinopathy.¹ In general, the growth and spread of tumors has been shown to be dependent on the development of increased vascularization in the tumor vicinity in order to maintain sufficient oxygenation.¹ Tumor expression of proangiogenic factors, including VEGF, has been associated with advanced tumor progression in a number of human cancers.^2,3 Increased expression of VEGF has been associated with poorer prognosis in patients with cancer of the colon,^4-7 stomach,^8,9 pancreas,^10,11 breast,^12-15 ovary,^16,17 prostate,^18,19 liver,²⁰ and in oral squamous cell carcinoma²¹ and melanoma.²² Serum VEGF levels are significantly higher than plasma levels. This is thought to reflect the fact that VEGF is released into the serum from platelets as part of the clotting process.²³ It has been hypothesized that VEGF released from activated platelets may have a role in angiogenesis during wound healing and may also be associated with pathological conditions, such as atherosclerosis, tumor growth, and metastasis formation.²³ In different studies, serum VEGF^{7,16,17,20,21} and plasma VEGF^6,12,18,19 levels have been found to correlate with the clinical status of patients with cancer.

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2. Nagy JA, Vasile E, Feng D, et al. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med. 2002 Dec 2; 196(11):1497-1506. PubMed 12461084

3. Reinmuth N, Parikh AA, Ahmad SA, et al. Biology of angiogenesis in tumors of the gastrointestinal tract. Microsc Res Tech. 2003 Feb 1; 60(2):199-207. PubMed 12539174

4. Lee JC, Chow NH, Wang ST, Huang SM. Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer. 2000 Apr; 36(6):748-753. PubMed 10762747

5. Takahashi Y, Kitadai Y, Bucana CD, Cleary KR, Ellis LM. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995 Sep 15; 55(18):3964-3968. PubMed 7664263

6. Minagawa N, Nakayama Y, Hirata K, et al. Correlation of plasma level and immunohistochemical expression of vascular endothelial growth factor in patients with advanced colorectal cancer. Anticancer Res. 2002 Sep-Oct; 22(5):2957-2963. PubMed 12530025

7. Chin KF, Greenman J, Reusch P, Gardiner E, Marme D, Monson JR. Vascular endothelial growth factor and soluble Tie-2 receptor in colorectal cancer: Associations with disease recurrence. Eur J Surg Oncol. 2003 Aug; 29(6):497-505. PubMed 12875855

8. Takahashi Y, Cleary KR, Mai M, Kitadai Y, Bucana CD, Ellis LM. Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer. Clin Cancer Res. 1996 Oct; 2(10):1679-1684. PubMed 9816116

9. Maeda K, Kang SM, Onoda N, et al. Vascular endothelia growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric carcinoma. Cancer. 1999 Aug 15; 86(4):566-571. PubMed 10440683

10. Fujimoto K. Hosotani R, Wada M, et al. Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis. Eur J Cancer. 1998 Aug; 34(9):1439-1447. PubMed 9849429

11. Ikeda N. Adachi M, Taki T, et al. Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer. 1999 Mar; 79(9-10):1553-1563. PubMed 10188906

12. Adams J, Carder PJ, Downey S, et al. Vascular endothelial growth factor (VEGF) in breast cancer: Comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. Cancer Res. 2000 Jun 1; 60(11):2898-2905. PubMed 10850435

13. Berns EM, Klijn JG, Look MP, et al. Combined vascular endothelial growth factor and TP53 status predicts poor response to tamoxifen therapy in estrogen receptor-positive advance breast cancer. Clin Cancer Res. 2003 Apr; 9(4):1253-1258. PubMed 12684392

14. Manders P, Beex LV, Tjan-Heijnen VC, et al. The prognostic value of vascular endothelial growth factor in 574 node-negative breast cancer patients who did not receive adjuvant systemic therapy. Br J Cancer. 2002 Sep 23; 87(7):772-778. PubMed 12232762

15. Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y. Clinical relevance of amphiregulin and VEGF in primary breast cancers. Int J Cancer. 2004 Sep 20; 111(5):733-740. PubMed 15252843

16. Cooper BC, Ritchie JM, Broghammer CL, et al. Preoperative serum vascular endothelial growth factor levels: Significance in ovarian cancer. Clin Cancer Res. 2002 Oct; 8(10):3193-3197. PubMed 12374688

17. Alvarez Secord A, Sayer R, Snyder SA, et al. The relationship between serum vascular endothelial growth factor, persistent disease, and survival at second-look laparotomy in ovarian cancer. Gynecol Oncol. 2004 Jul; 94(1):74-79. PubMed 15262122

18. Duque JL, Loughlin KR, Adam RM, Kantoff PW, Zurakowski D, Freeman MR. Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer. Urology. 1999 Sep; 54(3):523-527. PubMed 10475365

19. George DJ, Halabi S, Shepard TF, et al. Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res. 2001 Jul; 7(7):1932-1936. PubMed 11448906

20. 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 Jun 15; 63(12):3121-3126. PubMed 12810638

21. Shang ZJ, Li JR, Li ZB. Circulating levels of vascular endothelial growth factor in patients with oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2002 Oct; 31(5):495-498. PubMed 12418564

22. Gorski DH, Leal AD, Goydos JS. Differential expression of vascular endothelial growth factor-A isoforms at different stages of melanoma progression. J Am Coll Surg. 2003 Sep; 197(3):408-418. PubMed 12946796

23. Wartiovaara U, Salven P, Mikkola H, et al. Peripheral blood platelets express VEGF-C and VEGF which are released during platelet activation. Thromb Haemost. 1998 Jul; 80(1):171-175. PubMed 9684805