Assessing the Diagnostic Value of VEGF Levels in Differentiation of Malignant Serous Discharge (Positive Cytology) from Benign Serous Discharge (Negative Cytology) Using ELISA Method

Document Type : Original Article (s)

Authors

1 Associate Professor, Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Student of Medicine, School of Medicine And Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: One of the factors effective on tumor cell growth and proliferation is vascular endothelial cell growth factor (VEGF). It also affects the formation of serous fluids such as ascites or pleural effusion through vascular permeability. However, detection and differentiation of malignant serous fluids from benign serous fluids have always been a problem. Therefore, the present study aimed to assess the diagnostic value and level of VEGF in differentiation of malignant serous fluids from benign serous fluids.Methods: This descriptive, analytical case-control study was conducted on 92 serous fluid (ascites and pleural effusion) samples from the pathology ward of Alzahra Hospital (Iran). The study employed enzyme-linked immunosorbent assay (ELISA) to evaluate samples. The samples were divided into 2 groups (n = 46 in each) of malignant serous fluids (positive cytology) and benign serous fluids (negative cytology). VEGF levels were examined in both groups. The data was analyzed using independent t-test and chi-square test.Findings: In the malignant effusion group, there were 22 males and 24 females with the mean age of 56.47 ± 14.57 years. In the benign effusion group, there were 30 males and 16 females with the mean age of 57.95 ± 17.07 years. The mean VEGF levels in the malignant effusion and benign effusion groups were 753.71 ± 6.61 and 143.99 ± 1.27 pg/ml, respectively. In addition, VEGF levels in the group with malignant serous discharge were significantly higher compared to the group with benign serous discharge (P = 0.02).Conclusion: The results of the present study showed that VEGF can be used as a biochemical factor in differentiation of malignant serous fluids (positive cytology) from benign serous fluids (negative cytology).

Keywords


  1. Makrilia N, Lappa T, Xyla V, Nikolaidis I, Syrigos K. The role of angiogenesis in solid tumours: an overview. Eur J Intern Med 2009; 20(7): 663-71.
  2. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992; 267(16): 10931-4.
  3. Zhai Y, Ni J, Jiang GW, Lu J, Xing L, Lincoln C, et al. VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo. FASEB J 1999; 13(1): 181-9.
  4. Strizzi L, Catalano A, Vianale G, Orecchia S, Casalini A, Tassi G, et al. Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol 2001; 193(4): 468-75.
  5. Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, et al. Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res 2001; 61(15): 5736-40.
  6. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9(6): 669-76.
  7. Kerbel RS. Tumor angiogenesis. N Engl J Med 2008; 358(19): 2039-49.
  8. Gupta K, Zhang J. Angiogenesis: a curse or cure? Postgrad Med J 2005; 81(954): 236-42.
  9. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 1991; 5(12): 1806-14.
  10. Suto K, Yamazaki Y, Morita T, Mizuno H. Crystal structures of novel vascular endothelial growth factors (VEGF) from snake venoms: insight into selective VEGF binding to kinase insert domain-containing receptor but not to fms-like tyrosine kinase-1. J Biol Chem 2005; 280(3): 2126-31.
  11. Connolly DT. Vascular permeability factor: a unique regulator of blood vessel function. J Cell Biochem 1991; 47(3): 219-23.
  12. Hlatky L, Tsionou C, Hahnfeldt P, Coleman CN. Mammary fibroblasts may influence breast tumor angiogenesis via hypoxia-induced vascular endothelial growth factor up-regulation and protein expression. Cancer Res 1994; 54(23): 6083-6.
  13. Senger DR, Van de Water L, Brown LF, Nagy JA, Yeo KT, Yeo TK, et al. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev 1993; 12(3-4): 303-24.
  14. Hamed EA, El-Noweihi AM, Mohamed AZ, Mahmoud A. Vasoactive mediators (VEGF and TNF-alpha) in patients with malignant and tuberculous pleural effusions. Respirology 2004; 9(1): 81-6.
  15. Kalomenidis I, Kollintza A, Sigala I, Papapetropoulos A, Papiris S, Light RW, et al. Angiopoietin-2 levels are elevated in exudative pleural effusions. Chest 2006; 129(5): 1259-66.
  16. Economidou F, Antoniou KM, Tzanakis N, Sfiridaki K, Siafakas NM, Schiza SE. Angiogenic molecule Tie-2 and VEGF in the pathogenesis of pleural effusions. Respir Med 2008; 102(5): 774-9.
  17. Garrison RN, Kaelin LD, Galloway RH, Heuser LS. Malignant ascites. Clinical and experimental observations. Ann Surg 1986; 203(6): 644-51.
  18. Zebrowski BK, Liu W, Ramirez K, Akagi Y, Mills GB, Ellis LM. Markedly elevated levels of vascular endothelial growth factor in malignant ascites. Ann Surg Oncol 1999; 6(4): 373-8.
  19. Momi H, Matsuyama W, Inoue K, Kawabata M, Arimura K, Fukunaga H, et al. Vascular endothelial growth factor and proinflammatory cytokines in pleural effusions. Respir Med 2002; 96(10): 817-22.
  20. Light RW, Macgregor MI, Luchsinger PC, Ball WC, Jr. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972; 77(4): 507-13.
  21. Folkman J, Watson K, Ingber D, Hanahan D. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 1989; 339(6219): 58-61.
  22. Folkman J. Endothelial cells and angiogenic growth factors in cancer growth and metastasis. Introduction. Cancer Metastasis Rev 1990; 9(3): 171-4.
  23. Daniil ZD, Zintzaras E, Kiropoulos T, Papaioannou AI, Koutsokera A, Kastanis A, et al. Discrimination of exudative pleural effusions based on multiple biological parameters. Eur Respir J 2007; 30(5): 957-64.
  24. Cheng D, Lee YC, Rogers JT, Perkett EA, Moyers JP, Rodriguez RM, et al. Vascular endothelial growth factor level correlates with transforming growth factor-beta isoform levels in pleural effusions. Chest 2000; 118(6): 1747-53.
  25. Kaya A, Poyraz B, Celik G, Ciledag A, Gulbay BE, Savas H, et al. Vascular endothelial growth factor in benign and malignant pleural effusions. Arch Bronconeumol 2005; 41(7): 376-9.
  26. Kraft A, Weindel K, Ochs A, Marth C, Zmija J, Schumacher P, et al. Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer 1999; 85(1): 178-87.
  27. Duysinx BC, Corhay JL, Hubin L, Nguyen D, Henket M, Louis R. Diagnostic value of interleukine-6, transforming growth factor-beta 1 and vascular endothelial growth factor in malignant pleural effusions. Respir Med 2008; 102(12): 1708-14.
  28. Hirayama N, Tabata C, Tabata R, Maeda R, Yasumitsu A, Yamada S, et al. Pleural effusion VEGF levels as a prognostic factor of malignant pleural mesothelioma. Respir Med 2011; 105(1): 137-42.
  29. Lee YCG. Cytokines in pleural diseases. In: Light RW, Le YCG, editors. Textbook of pleural disease. 1st ed. London: Hodder Arnold Publishers; 2003. p. 63-89.
  30. Toi M, Inada K, Suzuki H, Tominaga T. Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and the association with vascular endothelial growth factor expression. Breast Cancer Res Treat 1995; 36(2): 193-204.
  31. Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 1996; 77(5): 858-63.
  32. Neufeld G, Tessler S, Gitay-Goren H, Cohen T, Levi BZ. Vascular endothelial growth factor and its receptors. Prog Growth Factor Res 1994; 5(1): 89-97.
  33. Shinkaruk S, Bayle M, Lain G, Deleris G. Vascular endothelial cell growth factor (VEGF), an emerging target for cancer chemotherapy. Curr Med Chem Anticancer Agents 2003; 3(2): 95-117.
  34. Yamamoto S, Konishi I, Mandai M, Kuroda H, Komatsu T, Nanbu K, et al. Expression of vascular endothelial growth factor (VEGF) in epithelial ovarian neoplasms: correlation with clinicopathology and patient survival, and analysis of serum VEGF levels. Br J Cancer 1997; 76(9): 1221-7.