Vascular Endothelial Growth Factor

CPT: 83520
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Synonyms

  • VEGF-A, Serum

Expected Turnaround Time

3 - 5 days


Related Documents


Specimen Requirements


Specimen

Serum


Volume

0.5 mL


Container

Red-top tube or gel-barrier tube


Collection

Transfer the serum into a Labcorp PP transpak frozen purple tube with screw cap (Labcorp No. 49482). Freeze immediately and maintain frozen until tested. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.


Storage Instructions

Freeze.


Stability Requirements

Temperature

Period

Room temperature

Unstable

Refrigerated

Unstable

Frozen

14 days

Freeze/thaw cycles

Stable x3


Causes for Rejection

Nonserum specimen received; nonfrozen specimen; gross hemolysis or lipemia


Test Details


Use

This test is used for measurement of vascular endothelial growth factor levels in serum.


Limitations

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Elevated circulating concentrations of vascular endothelial growth factor (VEGF) may be observed in a variety of disease states, especially those associated with angiogenesis. Elevated concentrations of VEGF must be interpreted within the clinical context of the patient.

Normal concentrations of VEGF do not exclude the diagnosis of POEMS.

The presence of bevacizumab in patient serum interferes with detection of VEGF. Caution should be taken while interpreting results of patients receiving bevacizumab therapy.


Methodology

Enzyme immunoassay (EIA)


Reference Interval

62−707 pg/mL


Additional Information

Vascular endothelial growth factor (VEGF) is a homodimeric 34 to 45 kilodalton, heparin-binding glycoprotein. VEGF has potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells.1,2 VEGF expression is regulated by hypoxia, with levels increasing when cells detect an environment low in oxygen. Physiologically, VEGF induces new blood vessel formation during embryonic development, after tissue injury and in response to blocked vessels. 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.1,3

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder, which is most commonly lambda restricted.4 The neurological hallmark, which forms one of the mandatory criteria for diagnosis, is a subacute onset demyelinating neuropathy, which can be rapidly disabling and painful. Elevated VEGF is highly specific for POEMS syndrome (though not pathognomonic) and thought to be involved in the pathophysiology of systemic features including organomegaly and volume overload. VEGF levels reflect disease activity, falling with treatment and rising with disease progression or relapse. Monitoring VEGF levels may be useful as a disease prognostic marker.5

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.1,6 Tumor expression of proangiogenic factors, including VEGF, has been associated with advanced tumor progression in a number of human cancers.7,8 Increased expression of VEGF has been associated with poorer prognosis in patients with cancer of the colon,9-11 stomach,12-14 pancreas,15,16 breast,17-20 ovary,21,22 prostate,23,24 liver,25 oral squamous cell,26 bone27 and in melanoma.28 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.29 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.29 In different studies, serum VEGF12,21,22,25,26 and plasma VEGF11,17,23,24 levels have been found to correlate with the clinical status of patients with cancer.


Footnotes

1. Parikh AA, Ellis LM. The vascular endothelial growth factor family and its receptors. Hematol Oncol Clin North Am. 2004 Oct;18(5):951-971,vii.15474329
2. Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell. 2019 Mar 7;176(6):1248-1264.30849371
3. Ding R, Zhu S, Zhao X, Yue R. Vascular endothelial growth factor levels in diabetic peripheral neuropathy: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023 May 12;14:1169405.37251664
4. Dispenzieri A. POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management. Am J Hematol. 2019 Jul;94(7):812-827.31012139
5. Misawa S, Sato Y, Katayama K, et al. Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study. BMJ Open. 2015 Nov 11;5(11):e009157.26560063
6. Siveen KS, Prabhu K, Krishnankutty R, et al. Vascular endothelial growth factor (VEGF) signaling in tumour vascularization: potential and challenges. Curr Vasc Pharmacol. 2017;15(4):339-351.28056756
7. 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):1497-1506.12461084
8. 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):199-207.12539174
9. 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):748-753.10762747
10. 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):3964-3968.7664263
11. 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):2957-2963.12530025
12. 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):497-505.12875855
13. 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):1679-1684.9816116
14. 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):566-571.10440683
15. 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):1439-1447.9849429
16. Ikeda N, Adachi M, Taki T, et al. Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer. 1999 Mar;79(9-10):1553-1563.10188906
17. 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):2898-2905.10850435
18. 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):1253-1258.12684392
19. 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):772-778.12232762
20. 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):733-740.15252843
21. 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):3193-3197.12374688
22. 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):74-79.15262122
23. 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):523-527.10475365
24. 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 CancerRes. 2001 Jul;7(7):1932-1936.11448906
25. 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):3121-3126.12810638
26. 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):495-498.12418564
27. Zhang C, Wang L, Xiong C, Zhao R, Liang H, Luo X. The role of vascular endothelial growth factor as a prognostic and clinicopathological marker in osteosarcoma: a systematic review and meta-analysis. J Orthop Surg Res. 2021 Dec 28;16(1):738.34963495
28. 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):408-418.12946796
29. 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):171-175.9684805

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
117021 VEGF, Serum 34694-0 117067 VEGF, Serum pg/mL 34694-0

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