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Virchows Archiv

, Volume 439, Issue 5, pp 645–652 | Cite as

Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomas

  • Bernhard Hemmerlein
  • Alexander Kugler
  • Rehyan Özisik
  • Rolf-Hermann Ringert
  • Heinz-Joachim Radzun
  • Paul Thelen
Original Article

Abstract

Rapidly growing tumors often develop necrosis. In the present study the expression of vascular endothelial growth factor (VEGF) was investigated and compared to microvessel density and necrosis of renal cell carcinomas. In the tumor-host interface the microvessel density was significantly increased compared to central tumor areas. Tumor necrosis was associated with a decrease of microvessel density and an increase of the VEGF protein expression within the perinecrotic rim. VEGF protein was focally upregulated in vital tumor tissue. An increase of the apoptotic rate of endothelia and vital tumor tissue in tumors with necrosis could not be detected. VEGF(121,165) mRNA was decreased in proliferatively active carcinomas compared to less proliferative tumors. Multicellular renal cell cancer spheroids as a model of chronic hypoxia developed central apoptosis but no necrosis. VEGF was upregulated in the spheroid. Tumor microvessels expressed matrix metalloproteinase -2 and -9 and an incomplete pericyte covering in comparison to tumor-free tissue indicating immature active angiogenesis. We conclude that highly proliferative renal cell carcinomas outgrow their vascular supply and develop chronic hypoxia inducing a decrease of proliferation and an increase of VEGF expression. However, chronic hypoxia does not cause significant necrosis or apoptosis. Tumor necrosis is more likely induced by acute hypoxia due to immature microvessels. Furthermore, VEGF expression associated with concomitant tumor necrosis may help identify renal cell carcinomas susceptible to antiangiogenic therapy.

Microvessel density Tumor necrosis VEGF expression 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Bernhard Hemmerlein
    • 1
  • Alexander Kugler
    • 2
  • Rehyan Özisik
    • 1
  • Rolf-Hermann Ringert
    • 2
  • Heinz-Joachim Radzun
    • 1
  • Paul Thelen
    • 2
  1. 1.Department of Pathology, Georg-August University, Medizinische Fakultät, Robert-Koch-Str. 40, 37075 GöttingenGermany
  2. 2.Department of Urology, Georg-August University, Medizinische Fakultät, 37075 GöttingenGermany

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