Abstract
Background and aims
Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis and increases vascular permeability. Epidermal growth factor (EGF) induces proliferation of epidermal cells and stimulates epidermal migration. Increased VEGF and EGF expression have been associated with poor clinical outcome in many malignancies. Several recent reports have shown overexpression of VEGF and EGF in papillary thyroid cancer (PTC). The study aimed to determine the intensity of expression of VEGF and EGF in patients with PTC and to find any correlation between the intensity of the expression and staging of the disease at the moment of surgery
Patients and methods
The study comprised a group of 48 consecutive patients with PTC who underwent radical surgery. The group consisted of 11, 25, eight and four patients at pT1N0M0, pT2N0M0, pT3N1M0 and pT4N1M0 stages, respectively. The control group was composed of 20 healthy bone marrow transplant donors, age-, gender- and BMI-matched with PTC patients. The immuno-chemiluminescence enzyme linked immunoassay (ELISA) method was used to determine the expression and level of VEGF and EGF in serum samples. Patients’ characteristics, serum levels of VEGF and EGF, final histology and pTNM were analysed.
Results
The mean serum level of VEGF and EGF was remarkably higher in PTC patients than in controls. A negative correlation between staging in pTNM classification and the mean serum VEGF level (r=−0.5168; P<0.05) as well as a positive correlation between staging in pTNM classification and the mean serum EGF level (r=0.6104; P<0.05) in PTC patients was observed.
Conclusions
Both VEGF and EGF play an important role in PTC growth. However, the intensity of their expression is variable, depending on the stage of the disease. The highest intensity of VEGF expression is characteristic for low-stage T1N0M0 disease, whereas the highest intensity of EGF expression is more often found at locally advanced pT3 and pT4N1M0 stages of the disease. Further long-term follow-up studies are required to demonstrate the prognostic value of VEGF and EGF in PTC, particularly in identification of patients with expected poor prognosis or shorter recurrence-free survival.
Similar content being viewed by others
References
American Cancer Society (1991) Cancer Stat 41:28–29
DeGroot LJ, Kaplan EL, McCormik M, Straus FH (1990) Natural history, treatment and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 71:414–424
Schindler AM, van Melle G, Evequoz B, Scazziga B (1991) Prognostic factors in papillary carcinoma of the thyroid. Cancer 68:324–330
Goretzki PE, Simon D, Dotzenrath C, Schulte KM, Röher HD (2000) Growth regulation of thyroid and thyroid tumors in humans. World J Surg 24:913–922
Falk SA (1997) Thyroid disease: endocrinology, surgery, nuclear medicine and radiotherapy. Lippincott, Williams & Wilkins, Philadelphia
Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 359:843–848
Yancopoulos GD, Klagsburn M, Folkman J (1998) Vasculogenesis, angiogenesis and growth factors: ephrins enter the fray at the border. Cell 93:661–664
Risau W (1997) Mechanism of angiogenesis. Nature 386:671–674
Carmeliet P (2000) Mechanism of angiogenesis and arteriogenesis. Nat Med 6:389–395
Balkwill F (2003) Chemokines biology in cancer. Semin Immunol 15:49–55
Reichlin M (1998) Systemic lupus erythematosus. In: Rose NR, Mackay IR (eds) The autoimmune diseases. Academic, Philadelphia, pp 1–37
Norrby W (1997) Angiogenesis: a new aspect relating to its initiation and control. Acta Pathol Microbiol Immunol Scand 105:417–437
Eliseenko VI, Skobelkin OK, Chegin VM (1998) Microcirculation and angiogenesis during wound healing by first and second intention. Bull Exp Biol Med 105:289–292
Maeda K, Chung YS, Ogawa Y (1996) Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 77:858–863
Okada F, Rak J, St. Croix B, Lieubeau B, Kaya M, Roncari L, Shirasawa S, Sasazuki T, Kerbel RS (1998) Impact of oncogenes on tumor angiogenesis: mutant K-ras upregulation of VEGF/VPF is necessary but not sufficient for tumorigenicity of human colorectal carcinoma cells. Proc Natl Acad Sci 95:3609–3614
Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, Matsubara I, Vinante O, Bonoldi E, Boracchi P, Gatti C, Suzuki H, Tominaga T (1997) Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst 89:139–147
Goodman AL, Rone JD (1987) Thyroid angiogenesis: endotheliotropic chemoattractant activity from rat thyroid cell in culture. Endocrinology 121:2131–2140
Turner HE, Harris AL, Melmed SH, Wass JAH (2003) Angiogenesis in endocrine tumors. Endocr Rev 24:600–632
Rak J, Mrtsuhashi Y, Bayko L, Filmus J, Sasazuki T, Kerbel RS (1995) Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction or inhibition of tumor angiogenesis. Cancer Res 55:4575–4580
Kerbel RS, Vilona-Petit A, Okada F, Rak J (1998) Establishing a link between oncogenes and tumor angiogenesis. Mol Med 4:286–295
Lin SY, Wang YY, Sheu WH (2003) Preoperative plasma concentrations of vascular endothelial growth factor and matrix metalloproteinase 9 are associated with stage progression in papillary thyroid cancer. Clin Endocrinol 58:513–518
Lennard CM, Patel A, Wilson J, Reinhardt B, Tuman C, Fenton C, Blair E, Francis GL, Tuttle RM (2001) Intensity of vascular endothelial growth factor expression associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129:552–558
Huang SM, Lee JC, Wu TJ, Chow NH (2001) Clinical relevance of vascular endothelial growth factor for thyroid neoplasms. World J Surg 25:302–306
Westermark K, Westermark B (1982) Mitogenic effect of epidermal growth factor on sheep thyroid cells in culture. Exp Cell Res 138:47–55
Westermark K, Karlsson A, Westermark B (1985) Thyrotropin modulates EGF receptor function in porcine thyroid follicle cells. Mol Cell Endocrinol 40:17–23
Westermark K, Karlsson FA, Westermark B (1983) Epidermal growth factor modulates thyroid growth and function in culture. Endocrinology 112:1680–1686
Masuda H, Sugenoya A, Kobayashi S, Kasuga Y, Iida F (1988) Epidermal growth factor receptor on human thyroid neoplasm. World J Surg 12:616–622
Alslen LA, Myking AO, Salvesen H, Varhaug JE (1993) Prognostic impact of EGF-receptor in papillary thyroid carcinoma. Br J Cancer 68:808–812
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Konturek, A., Barczyński, M., Cichoń, S. et al. Significance of vascular endothelial growth factor and epidermal growth factor in development of papillary thyroid cancer. Langenbecks Arch Surg 390, 216–221 (2005). https://doi.org/10.1007/s00423-004-0529-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00423-004-0529-0