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Evaluation of serum vascular endothelial growth factor (VEGF) and microvessel density (MVD) as prognostic indicators in carcinoma breast

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Abstract

Purpose

Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide. A great deal of interest has been paid to the predictive value of neoangiogenesis represented by microvessel density (MVD), on clinical progression and prognosis of several types of tumors. Serum VEGF levels may therefore be clinically useful for the prediction of increase in tumor growth, metastasis or recurrence spread in individual patients.

Methods

A total of 265 cases of breast lesions were studied to note the importance of Serum VEGF as a prognostic marker in cases of breast carcinoma. The expressed serum VEGF levels and microvessel density (MVD) were assessed quantitatively and were correlated with tumor grade, tumor necrosis, stromal reaction and nodal metastasis.

Results

Serum VEGF was increased in patients with lesions of breast and the levels of serum VEGF in malignant lesions were significantly increased when compared to benign lesions. It was also noted that the levels of serum VEGF increased with increasing grades of malignancy. MVD showed a significant correlation in the early stages of the malignant tumors, where there was no necrosis, but in tumors associated with necrosis and hemorrhage MVD failed to show significant correlation.

Conclusion

Hence, serum vascular endothelial growth factor can be used as a more reliable, non-invasive adjunctive diagnostic criteria in the assessment of the grade and hence, the prognosis of malignant tumors of the breast.

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References

  • Amaya H, Tanigawa N, Lu C, Matsumura M, Shimomatsuya T, Horiuchi T, Murakoa R (1997) Association of vascular endothelial growth factor expression with tumor angiogenesis survival and thymidine phosphorylase/platelet derived endothelial cell growth factor expression in human colorectal cancer. Cancer Lett 119:227–235. 10.1016/S0304-3835(97)00280-2

    Google Scholar 

  • Auerbach A, Auergach R (1994) Angiogenesis, a review. Pharmacol Ther 63:265–311. doi:10.1016/0163-7258(94)90027-2

    Article  PubMed  CAS  Google Scholar 

  • Bamias A, Dimopoulos MA (2003) Angiogenesis in human cancer: implications in cancer therapy. Eur J Intern Med 459–469. 10.1016/j.ejim.2003.10.003

  • Bland KI, Beenken SW, Copeland EM III (2005) Epidemiology and natural history of breast cancer. In: Brunicardi FC, Anderson DR, Billiar TR, Dunn DL, Humter GH, Pollock RE (eds) Schwartz’s principle of surgery, 8th edn. McGraw-hill, New York, pp 471–472

    Google Scholar 

  • Boocock CA, Charnock-Jones DS, Charkey AM, McLaren J, Barker PJ, Wright KA et al (1995) Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma. J Natl Cancer Inst 87:506–516. doi:10.1093/jnci/87.7.506

    Article  PubMed  CAS  Google Scholar 

  • Brown LF, Verse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF (1993) Increased expression of vascular permeability factor (vascular endothelial growth factor and its receptors in kidney and bladder carcinomas. Am J Pathol 143:1255–1262

    PubMed  CAS  Google Scholar 

  • Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257. doi:10.1038/35025220

    Article  PubMed  CAS  Google Scholar 

  • Carmelite P (2000) Mechanism of angiogenesis and arteriogenesis. Nat Med 6:389–395. doi:10.1038/74651

    Article  CAS  Google Scholar 

  • Dameron KM, Volpert OV, Tainsky MA, Bouck N (1994) Control of angiogenesis in fibroblast by p53 regulation of thrombosponder-1. Science 265:1582–1584. doi:10.1126/science.7521539

    Article  PubMed  CAS  Google Scholar 

  • Devries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT (1992) The fins like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255:989–991. doi:10.1126/science.1312256

    Article  CAS  Google Scholar 

  • Dirix LY, Vermeulen PB, Hubens G, Benoy I, Martin M, De Pooter C et al (1996) Serum basic fibroblast factor and vascular endothelial growth factor and tumor growth kinetics in advanced colorectal cancer. Ann Oncol 7:843–848

    PubMed  CAS  Google Scholar 

  • Dirix LY, Vermeulen PB, Panwinski A, Prove A, Benoy I, De Pooter C et al (1997) Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients. Br J Cancer 76:238–243

    PubMed  CAS  Google Scholar 

  • Ferrara N (1996) The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat 36:127–137. doi:10.1007/BF00666035

    Article  Google Scholar 

  • Ferrara N, Smyth TD (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25. doi:10.1210/er.18.1.4

    Article  PubMed  CAS  Google Scholar 

  • Fidler IJ, Ellis LM (1994) The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 79:185–1888. doi:10.1016/0092-8674(94)90187-2

    Article  PubMed  CAS  Google Scholar 

  • Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM et al (2000) Prognostic factors in breast cancer: College of American Pathologist consensus statement. Arch Pathol Lab Med 124:966–978

    PubMed  CAS  Google Scholar 

  • Foekens JA, Peters HA, Grebenchtchikov N, Look MP, Meijer-van Gelder ME, Geurts-Moespot A et al (2001) High tumor levels of vascular endothelial growth factor predict poor response to systematic therapy in advanced breast cancer. Cancer Res 61:5407–5414

    PubMed  CAS  Google Scholar 

  • Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31. doi:10.1038/nm0195-27

    Article  PubMed  CAS  Google Scholar 

  • Fontanini G, Boldrini L, Chine S, Pisaturo F, Vignati F, Calcinai A et al (1999) Expression of vascular endothelial growth factor non-small cell lung carcinomas. Br J Cancer 79:363–369. doi:10.1038/sj.bjc.6690058

    Article  PubMed  CAS  Google Scholar 

  • Gasparni G, Weider N, Malutas S, Pooza F, Boracchi P, Mezzetti M, Testolin A, Bevilacqus P (1993) Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma. Int J Cancer 55:739–744. 10.1002/ijc.2910550507

    Google Scholar 

  • Goddard JC, Sutton CD, Berry DP (2001) The use of microvessel density assessment in human urological tumors. BJU Int 87(9):866–876. doi:10.1046/j.1464-410x.2001.02181.x

    Article  PubMed  CAS  Google Scholar 

  • Goddard JC, Sutton CD, Furness PN, Kockelbergh RC, P’Byne KJ (2002) A computer image analysis system for microvessel density measurement in solid tumors. Angiogenesis 5:15–20. doi:10.1023/A:1021518315757

    Article  PubMed  Google Scholar 

  • Greenlee RT, Murray T, Bolden S et al (2000) Cancer statistics 2000. CA Cancer J Clin 50:7–33. doi:10.3322/canjclin.50.1.7

    Article  PubMed  CAS  Google Scholar 

  • Hannen EJM, Riediger D (2004) The quantification of angiogenesis in relation to metastasis in oral cancer: a review. Int J Oral Maxillofac Surg 33:2–7. doi:10.1054/ijom.2003.0433

    Article  PubMed  CAS  Google Scholar 

  • Hannen EJM, Van der Lack JA, Manni JJ, Freihofer HP, Slootweg PJ, Loole R, De Wild PC et al (2002) Computer assisted analysis of the microvasculature in metastasized and non metastasized squamous cell carcinoma of the tongue. Head Neck 24:643–650. doi:10.1002/hed.10100

    Article  PubMed  Google Scholar 

  • Heide K, Schwick HG (1973) Preparation of globulin. Handbook of experimental biology, vol 1. Academic press, New York

  • Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW (1991) The vascular endothelial growth factor family: identification of fourth molecular species and characterization of alternative splicing. Mol Endocrinol 5:1806–1814

    Article  PubMed  CAS  Google Scholar 

  • Ikeda E, Achen MG, Breier G, Risau W (1995) Hypoxia-induces transcription; activiation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J Biol Chem 25:19761–19766

    Google Scholar 

  • Konecny GE, Meng YG, Untch M, Wang HJ, Bauerfeind I, Epstein M et al (2004) Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res 10:1706–1716. doi:10.1158/1078-0432.CCR-0951-3

    Article  PubMed  CAS  Google Scholar 

  • Li C, Shintani S, Terakado N, Llosek SK, Ishiokawa T, Nakashiro K et al (2005) Microvessel density and expression of vascular endothelial growth factors, basic fibroblastic growth factors in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 34:559–565. doi:10.1016/j.ijom.2004.10.016

    Article  PubMed  CAS  Google Scholar 

  • Linderholm B, Tavelin B, Grankvist K, Henriksson R (1998) Vascular endothelial growth factor is of high prognostic value in node negative breast cancer carcinoma. J Clin Oncol 16:3121–3128

    PubMed  CAS  Google Scholar 

  • Linderholm B, Tavelin B, Grankvist K, Henriksson R (1999) Does vascular endothelial growth factor (VEGF) predict local relapse and survival in radiotherapy-treated node-negative breast cancer? Br J Cancer 81:727–732. doi:10.1038/sj.bjc.6690755

    Article  PubMed  CAS  Google Scholar 

  • Poon RT, Fan ST, John W (2003) Clinical significance of angiogenesis in gastrointestinal cancers: a target for novel prognostic and therapeutic approaches. Ann Surg 238:9–28. doi:10.1097/00000658-200307000-00003

    Article  PubMed  Google Scholar 

  • Poon RT, Lau C, Pang R, Kelvin KN, Yuen J, Fan ST (2007) High serum vascular endothelial growth factor levels predict poor prognosis after radiofrequency ablation of hepatocellular carcinoma: importance of tumor biomarker in ablative therapies. Ann Surg Oncol 14:1835–1845. doi:10.1245/s10434-007-9366-z

    Article  PubMed  Google Scholar 

  • Rosai J (2004) Rosai and Ackerman’s surgical pathology. Elsevier Inc, St. Louis

  • Rustucci B, Borzacchiello G, Maiolino P, Martano M, Paciello O, Papparella S (2004) Expression of vascular endothelial growth factor receptor Flk-1 in canine mammary carcinoma. J Comp Pathol 130:99–104. doi:10.1016/j.jcpa.2003.07.001

    Article  CAS  Google Scholar 

  • Salven P, Teerenhovi L, Joensuu H (1997) A high pretreatment serum vascular endothelial growth factor concentration is associated with poor out come in non-Hodgkins lymphoma. Blood 90:3167–3172

    PubMed  CAS  Google Scholar 

  • Salven P, Ruotsalainen T, Mattson K, Joensuu H (1998) High pretreatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small lung cancer. Int J Cancer 17:144–146. doi:10.1002/(SICI)1097-0215(19980417)79:2<144::AID-IJC8>3.0.CO;2-T

    Article  Google Scholar 

  • Salven P, Perhoniemi V, Tykka H, Maenpaa H, Joensuu H (1999) Serum VEGF levels in women with a benign breast tumor or breast cancer. Breast Cancer Res Treat 53:161–166. doi:10.1023/A:1006178517505

    Article  PubMed  CAS  Google Scholar 

  • Senger DR, Galli SJ, Dvorack AM, Perrizzi CA, Harvey VS, Dvorak HT (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Sci Wash DC 219:983–985. doi:10.1126/science.6823562

    Article  CAS  Google Scholar 

  • Senger DR, Van De Water L, Brown LF, Nagy JA, Yeo T-K, Berse B et al (1993) Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev 12:303–324. doi:10.1007/BF00665960

    Article  PubMed  CAS  Google Scholar 

  • Terman BI, Dougher-vermazen M, Carrision ME, Dimitrov D, Armellino DC, Gospodarowicz D, Böhlen P (1992) Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 187:1579–1586. doi:10.1016/0006-291X(92)90483-2

    Google Scholar 

  • Tse GM, Lui PC, Lee CS, Kumg FY, Scolyer RA, Law BK, Lau TS, Karim R, Putti TC (2004) Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: a multicenter study of 185 cases. Hum Pathol 35:1053–1057. doi:10.1016/j.humpath.2004.01.023

    Article  PubMed  CAS  Google Scholar 

  • Tukahashi Y, Kitodai Y, Bucana CD, Cleary KR, Ellis M (1995) Expression of vascular endothelial growth factor and its receptors, KDR, correletes with vascular metastasis and proliferation of human colon cancer. Cancer Res 55:3964–3968

    Google Scholar 

  • Veikkola T, Karkkainen M, Claesson WL, Alitatlo K (2000) Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res 60:2002–2212

    Google Scholar 

  • Vermeulen PB, Gasparini G, Fox SB (1996) Quantification of angiogenesis in solid tumours: an international consensus on the methodology and criteria of evaluation. Eur J Cancer 32A(14):2474–2484. doi:10.1016/S0959-8049(96)00379-6

    Article  PubMed  CAS  Google Scholar 

  • Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med 324:1–8

    PubMed  CAS  Google Scholar 

  • Yamamoto S, Konishi I, Mandai M, Kuroda H, Komatsu T, Nanbu K et al (1997) Expression of vascular endothelial growth factor (VEGF) in epithelial ovarian neoplasm: correlation with cliniocopathology and patients survival and analysis of serum VEGF levels. Br J Cancer 76:1221–1227

    PubMed  CAS  Google Scholar 

  • Yamamoto Y, Toi M, Kondo S, Matsumoto T, Suzuki H, Kitamura M et al (1999) Concentrations of vascular endothelial growth factor in the sera of normal controls and cancer patients. Clin Cancer Res 2:821–826

    Google Scholar 

  • Yukihiro H, Shingo T, Koichi O, Mika K, Akihito H, Takeshi M et al (2005) Vascular endothelial growth factor level as a prognostic determinant of small cell lung cancer in Japanese patients. Intern Med 44:26–34. doi:10.2169/internalmedicine.44.26

    Article  Google Scholar 

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Acknowledgments

The authors thank for the financial support Project No. 2003/35/BRNS/616/Dated 14-07-03 from Department of Atomic energy, Board of Radiation and Isotope Technology, Baba Atomic Research Centre, Mumbai, JSS Medical College & Hospital for providing clinical material for the furtherance of this work. Mytheli Kameshwaran, Laboratory Nuclear Medicine Section, Bio-Medical Group, Bhabha Atomic Research center, Mumbai, Maharasthra, India.

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There is no conflict of interest.

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Authors and Affiliations

  1. Department of Applied Botany and Biotechnology, University of Mysore, Manasagangotri, Mysore, Karnataka, 570 006, India

    S. Shivakumar, B. T. Prabhakar & Bharathi P. Salimath

  2. Department of Pathology, JSS Medical College, Mysore, Karnataka, 570 015, India

    K. Jayashree

  3. Laboratory Nuclear Medicine Section, Bio-Medical Group, Bhabha Atomic Research Center, Mumbai, Maharasthra, India

    M. G. R. Rajan

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  1. S. Shivakumar
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  2. B. T. Prabhakar
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  3. K. Jayashree
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  4. M. G. R. Rajan
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  5. Bharathi P. Salimath
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Correspondence to Bharathi P. Salimath.

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S. Shivakumar and B. T. Prabhakar have contributed equally to this work.

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Shivakumar, S., Prabhakar, B.T., Jayashree, K. et al. Evaluation of serum vascular endothelial growth factor (VEGF) and microvessel density (MVD) as prognostic indicators in carcinoma breast. J Cancer Res Clin Oncol 135, 627–636 (2009). https://doi.org/10.1007/s00432-008-0497-9

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  • DOI: https://doi.org/10.1007/s00432-008-0497-9

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