The diagnostic significance and the assessment of the value of vascular endothelial growth factor as a marker for success of chemical pleurodesis in malignant pleural effusion

Dalokay Kilic, Alper Findikcioglu, Goknur Alver, Tolga Tatar, Hakan Akbulut, Ahmet Hatipoglu
DOI: 10.4236/jbise.2011.43030                

Abstract

Differential diagnosis of pleural effusion is an important issue, since the treatment modalities and prognosis strictly depend on early and correct diagnosis of the underlying etiology. We assessed the efficacy of vascular endothelial growth factor (VEGF) in the differential diagnosis of patients with malignant and non-malignant pleural diseases. And also is assessed of the VEGF as a marker for success of chemical pleurodesis in malignant pleural effusion. Pleural effusions of 40 patients with a mean age of 55 (range, 26 to 78 years) were examined. A total of 20 patients had malignant pleural effusion; malignant mesothelioma (n=7), lung cancer (n=5) and metastatic malignancies (n=8). Twenty patients had benign pleural effusion; fibrinous pleuritis (n=6), tuberculosis (n=3) empyema (n=5), congestive heart failure (n=3), and acute pancreatitis (n=3). Definitive diagnosis was obtained in all cases with blind or open pleural biopsy, and cytological examination. VEGF levels were determined by enzyme-linked immunosorbent assay. The VEGF level of pleural effusion was comparably higher in the malignant group. The mean level of VEGF in patients with malignant pleural effusions (21.7 ± 1.8 ng/ml) was significantly (P <0.001) higher than that of (13.2 ± 1.5 ng/ml) non-malignant effusions. No significant difference was found regarding the VEGF levels and histological types in malignant pleural effusions. Negative correlation was observed between success rate of pleurodesis and VEGF level of pleural effusion (p= 0.015). The measurement of VEGF levels in pleural effusion may be useful to differentiate malignant from nonmalignant pleural effusions. VEGF level may also be an important prognostic marker for effective treatment of the patients who had malignant pleural effusions with pleurodesis. It is important issue in here whether VEGF could be useful in prognostication of outcome of chemical pleurodesis or not.

Keywords

Malignant pleural effusion, pleural effusion, chemical pleurodesis, vascular endothelial growth factor

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Sahn, S.A. (1997) Pleural diseases related to metastatic malignancies. European Respiratory, 10, 1907-13. doi:10.1183/09031936.97.10081907
[2]	Fontanini, G., Vignati, S., Boldrini L., Chinè, S., Silvestri, V., Lucchi, M., Mussi, A., Angeletti, C.A., Bevilacqua, G. (1997) Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma. Cliical Cancer Research, 3, 861-5.
[3]	Yanagawa, H., Takeuchi, E., Suzuki, Y., Ohmoto, Y., Bando, H., and Sone, S. (1999) Vascular endothelial growth factor in with malignant pleural effusion associated with lung cancer. Cancer Immunology Immunotherapy, 48, 396-400. doi:10.1007/s002620050592
[4]	Rusch, V.W., and Venkatraman, E.S. (1999) Important prognostic factors in patients with malignant pleural meso- thelioma, managed surgically. Annalls of Thoraic Surgery, 68, 1799-804. doi:10.1016/S0003-4975(99)01038-3
[5]	Poe, R.H., Isreal, R.H., Utell, M.J. (1984) Sensitivity, spesificity, and predictive values of closed pleural biopsy. Arcives of Internal Medicine, 144, 325-8. doi:10.1001/archinte.144.2.325
[6]	Sahn, S.A. (1988) The pleura. The American Review of Respiratory Disease, 138, 184-234.
[7]	Lee, T.C.Y., Zhang, C., Aston R., Hintz, R., Jagirdar, J., Perle, M.A., Burt, M., and Rom, W.N. (1993) Normal hu- man mesothelial cells and mesothelioma cell lines ex- press insulin like growth factor I and associated mole- cules. Cancer Research, 53, 2858-64.
[8]	Harvey, P., Warn, S.A., Dobbin, S., Arakaki, N., Daiku- hara, Y., Jaurand, M.C., Warn, R.M. (1998) Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology. British Journal of Cancer, 77, 1052-9. doi:10.1038/bjc.1998.176
[9]	Cacciotti, P., Strizzi, L., Vianale, G., Iaccheri, L., Libener, R., Porta, C., Tognon, M., Gaudino, G., and Mutti, L. (2002) The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor. American Journal of Respirartory Cell and Molecular Biology, 26, 189-93.
[10]	Hensbergen, Y.V., Broxterman, H.J., Hanamaaijer, R., Jorna, A.S., van Lent, N.A., Verheul, H.M., Pinedo, H.M., and Hoekman, K. (2002) Soluble aminopeptidase N/CD13 in malignant and nonmalignant effusion and intratumoral fluid. Clinical Cancer Research, 8, 3747-54.
[11]	Yano, S., Shinohara, H., Herbst, R.S., Kuniyasu, H., Bucana, C.D., Ellis, L.M., and Fidler, I.J (2000) Production of experimental malignant pleural effusions is dependent on invasion of the pleura and expression of vascular en- dothelial growth factor/vascular permeability factor by human lung cancer cells. American Journal of Pathol- ogy, 157, 1893-903. doi:10.1016/S0002-9440(10)64828-6
[12]	Strizzi, L., Catalano, A., Vianale, G., Orecchia, S., Casal- ini, A., Tassi, G., Puntoni, R., Mutti, L., Procopio, A. (2001) Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. Jour- nal of Pathology, 193, 468-75. doi:10.1002/path.824
[13]	Thickett, D.R., Armstrong, L., and Millar, A.B. (1999) Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions. Thorax, 54, 707-10. doi:10.1136/thx.54.8.707
[14]	Ferrara, N. (1999) Molecular and biological properties of vascular endothelial growth factor. J. Mol. Med, 77, 527- 43. doi:10.1007/s001099900019
[15]	Matsuyama, W., Hashiguchi, T., Mizoguchi, A., Iwami, F., Kawabata, M., Arimura, K., and Osame, M. (2000) Serum levels of vascular endothelial growth factor dependent on the stage progression of lung cancer. Chest, 118, 948-51. doi:10.1378/chest.118.4.948
[16]	Mattern, J., Koomagi, R., and Volm, M. (1997) Coexpression of VEGF and bFGF in human epidermoid lung carcinoma is associated with increased vessel density. Anti- cancer Research, 17, 2249-52.
[17]	Eroglu, A., Demirci, S., Ayyildiz, A., Kocaoglu, H., Akbulut, H., Akgul, H., and Elhan, H.A. (1999) Serum concentration of vascular endothelial growth factor and nitrite as an estimate of in vivo nitric oxide in patients with gastric cancer. British ournal of. Cancer, 80, 1630-4. doi:10.1038/sj/bjc/6690573
[18]	Akbulut, H., Altuntas, F., Akbulut, K.C., Ozturk, G., Cindoruk, M., Unal, E., and Icli, F. (2002) Prognostic role of serum vascular endothelial growth factor, basic fibroblast growth and nitrit oxide in patients with colorectel carcinoma. Cytokine, 20, 184-90. doi:10.1006/cyto.2002.1993
[19]	Paradise, V., Lagha, N.B., and Zeimoura, L. (2000) Expression of vascular endothelial growth factor in renal cell carcinomas. Virchows Archiv, 436, 351-6. doi:10.1007/s004280050458
[20]	Lim, S.C., Jung, S.I., Kim, Y.C., and Park, K.O. (2000) Vascular endothelial growth factor in malignant and tu- berculous pleural effusions. Journal of Korean Medicine Science, 15, 279-83.
[21]	Nehls, V., and Herrmann, R. (1998) The configuration of fibrin clots determines capillary morphogenesis and endo- thelial cell migration. Microvascular Research, 2, 9-20.
[22]	Taichman, N.S., Young, S., Cruchley, A.T., Taylor, P., and Paleolog, E. (1997) Human neutrophils secrete vascular endothelial growth factor. Journal of Leukocyte Biology, 62, 397-400.
[23]	Masood, R., Tong, Zheng, J.C., Smith, D.L., Hinton, D.R., and Gill, P.S. (2001) Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors. Blood, 98, 1904-1913. doi:10.1182/blood.V98.6.1904
[24]	Verheul, H.M.W., Hoekman, K., Jorna, A.S., Smit, E.F., and Pinedo, H.M. (2000) Targeting vascular endothelial growth factor blockade: Ascites and pleural effusion formation. The Oncologist, 5 (suppl 1), 45-50. doi:10.1634/theoncologist.5-suppl_1-45