Human Pathology
Volume 41, Issue 3 , Pages 375-384 , March 2010

Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays

  • Janice M. Mehnert

      Affiliations

    • Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA
    • Corresponding Author InformationCorresponding author. The Cancer Institute of New Jersey, 195 Little Albany Street Rm 5543, New Brunswick, NJ 08903.
  • ,
  • Mary M. McCarthy

      Affiliations

    • Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA
  • ,
  • Lucia Jilaveanu

      Affiliations

    • Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA
  • ,
  • Keith T. Flaherty

      Affiliations

    • Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
  • ,
  • Saadia Aziz

      Affiliations

    • Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA
  • ,
  • Robert L. Camp

      Affiliations

    • Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
  • ,
  • David L. Rimm

      Affiliations

    • Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
  • ,
  • Harriet M. Kluger

      Affiliations

    • Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA

Received 16 May 2009 ,Revised 10 August 2009 ,Accepted 18 August 2009.

References 

  1. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2008. CA Cancer J Clin. 2008;58:71–96
  2. Jain RK, Duda DG, Clark JW, Loeffler JS. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol. 2006;3:24–40
  3. Escudier B, Koralewski P, Pluzanska A, et al. A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-a2a vs placebo/interferon- a2a as first-line therapy in metastatic renal cell carcinoma. (Abstract) J Clin Oncol. 2007;25:2s
  4. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–676
  5. Einspahr JG, Thomas TL, Saboda K, et al. Expression of vascular endothelial growth factor in early cutaneous melanocytic lesion progression. Cancer. 2007;110:2519–2527
  6. Erhard H, Rietveld FJ, van Altena MC, Brocker EB, Ruiter DJ, de Waal RM. Transition of horizontal to vertical growth phase melanoma is accompanied by induction of vascular endothelial growth factor expression and angiogenesis. Melanoma Res. 1997;7(Suppl 2):S19–S26
  7. Straume O, Akslen LA. Expression of vascular endothelial growth factor, its receptors (FLT-1, KDR) and TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas. Am J Pathol. 2001;159:223
  8. Vlaykova T, Laurila P, Muhonen T, et al. Prognostic value of tumour vascularity in metastatic melanoma and association of blood vessel density with vascular endothelial growth factor expression. Melanoma Res. 1999;9:59–68
  9. Simonetti O, Lucarini G, Brancorsini D, et al. Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions. Cancer. 2002;95:1963–1970
  10. Demirkesen C, Buyukpinarbasili N, Ramazanoglu R, Oguz O, Mandel NM, Kaner G. The correlation of angiogenesis with metastasis in primary cutaneous melanoma: a comparative analysis of microvessel density, expression of vascular endothelial growth factor and basic fibroblastic growth factor. Pathology. 2006;38:132–137
  11. Bayer-Garner IB, Hough AJ, Smoller BR. Vascular endothelial growth factor expression in malignant melanoma: prognostic versus diagnostic usefulness. Mod Pathol. 1999;12:770–774
  12. Potti A, Moazzam N, Tendulkar K, Javed NA, Koch M, Kargas S. Immunohistochemical determination of vascular endothelial growth factor (VEGF) overexpression in malignant melanoma. Anticancer Res. 2003;23(5A):4023–4026
  13. Gitay-Goren H, Halaban R, Neufeld G. Human melanoma cells but not normal melanocytes express vascular endothelial growth factor receptors. Biochem Biophys Res Commun. 1993;190:702–708
  14. Graeven U, Fiedler W, Karpinski S, et al. Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR. J Cancer Res Clin Oncol. 1999;125:621–629
  15. Pisacane AM, Risio M. VEGF and VEGFR-2 immunohistochemistry in human melanocytic naevi and cutaneous melanomas. Melanoma Res. 2005;15:39–43
  16. Wobser M, Siedel C, Schrama D, Brocker EB, Becker JC, Vetter-Kauczok CS. Expression pattern of the lymphatic and vascular markers VEGFR-3 and CD31 does not predict regional lymph node metastasis in cutaneous melanoma. Arch Dermatol Res. 2006;297:352–357
  17. Clarijs R, Schalkwijk L, Hofmann UB, Ruiter DJ, de Waal RM. Induction of vascular endothelial growth factor receptor-3 expression on tumor microvasculature as a new progression marker in human cutaneous melanoma. Cancer Res. 2002;62:7059–7065
  18. Mouawad R, Spano JP, Comperat E, Capron F, Khayat D. Tumoural expression and circulating level of VEGFR-3 (Flt-4) in metastatic melanoma patients: correlation with clinical parameters and outcome. Eur J Cancer. 2009;45:1407–1414
  19. Camp RL, Chung GG, Rimm DL. Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med. 2002;8:1323–1327
  20. McCarthy MM, Divito KA, Sznol M, et al. Expression of tumor necrosis factor–related apoptosis-inducing ligand receptors 1 and 2 in melanoma. Clin Cancer Res. 2006;12:3856–3863
  21. Jilaveanu L, Zito C, Lee SJ, Nathanson KL, Camp RL, Rimm DL, et al. Expression of sorafenib targets in melanoma patients treated with carboplatin, paclitaxel and sorafenib. Clin Cancer Res. 2009;15:1076–1085
  22. Liu C, Okruzhnov Y, Li H, Nicholas J. Human herpesvirus 8 (HHV-8)-encoded cytokines induce expression of and autocrine signaling by vascular endothelial growth factor (VEGF) in HHV-8-infected primary-effusion lymphoma cell lines and mediate VEGF-independent antiapoptotic effects. J Virol. 2001;75:10933–10940
  23. Sini P, Samarzija I, Baffert F, et al. Inhibition of multiple vascular endothelial growth factor receptors (VEGFR) blocks lymph node metastases but inhibition of VEGFR-2 is sufficient to sensitize tumor cells to platinum-based chemotherapeutics. Cancer Res. 2008;68:1581–1592
  24. Hirakawa S, Kodama S, Kunstfeld R, Kajiya K, Brown LF, Detmar M. VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med. 2005;201:1089–1099
  25. Graells J, Vinyals A, Figueras A, et al. Overproduction of VEGF concomitantly expressed with its receptors promotes growth and survival of melanoma cells through MAPK and PI3K signaling. J Invest Dermatol. 2004;123:1151–1161
  26. Lacal PM, Ruffini F, Pagani E, D'Atri S. An autocrine loop directed by the vascular endothelial growth factor promotes invasiveness of human melanoma cells. Int J Oncol. 2005;27:1625–1632
  27. Flaherty KT, Schiller J, Schuchter LM, et al. A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel. Clin Cancer Res. 2008;14:4836–4842
  28. Hauschild A, Agarwala SS, Trefzer U, et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol. 2009;27:2823–2830
  29. Fruehauf JP, Lutzky J, McDermott DF, et al. Axitinib (AG-013736) in patients with metastatic melanoma: a phase II study. (Abstract) J Clin Oncol. 2008;26:(May 20 suppl); abstr 9006
  30. Ugurel S, Rappl G, Tilgen W, Reinhold U. Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. J Clin Oncol. 2001;19:577–583
  31. Tas F, Duranyildiz D, Oguz H, Camlica H, Yasasever V, Topuz E. Circulating serum levels of angiogenic factors and vascular endothelial growth factor receptors 1 and 2 in melanoma patients. Melanoma Res. 2006;16:405–411
  32. Brennecke S, Deichmann M, Naeher H, Kurzen H. Decline in angiogenic factors, such as interleukin-8, indicates response to chemotherapy of metastatic melanoma. Melanoma Res. 2005;15:515–522
  33. Osella-Abate S, Quaglino P, Savoia P, Leporati C, Comessatti A, Bernengo MG. VEGF-165 serum levels and tyrosinase expression in melanoma patients: correlation with the clinical course. Melanoma Res. 2002;12:325–334
  34. Hormbrey E, Gillespie P, Turner K, et al. A critical review of vascular endothelial growth factor (VEGF) analysis in peripheral blood: is the current literature meaningful?. Clin Exp Metastasis. 2002;19:651–663
  35. Webb NJ, Bottomley MJ, Watson CJ, Brenchley PE. Vascular endothelial growth factor (VEGF) is released from platelets during blood clotting: implications for measurement of circulating VEGF levels in clinical disease. Clin Sci (Lond). 1998;94:395–404
  36. Sabatino M, Kim-Schulze S, Panelli MC, et al. Serum vascular endothelial growthfactor and fibronectin predict clinical response to high-dose interleukin-2 therapy. J Clin Oncol. 2009;27:2645–2652

 Supported by NIH grant CA115756-01 (to H Kluger).

PII: S0046-8177(09)00299-8

doi: 10.1016/j.humpath.2009.08.016

Human Pathology
Volume 41, Issue 3 , Pages 375-384 , March 2010