, Volume 6, Issue 4, pp 295–301 | Cite as

Increased Expression of VEGF-Receptors (FLT-1, KDR, NRP-1) and Thrombospondin-1 is Associated with Glomeruloid Microvascular Proliferation, an Aggressive Angiogenic Phenotype, in Malignant Melanoma

  • Oddbjørn Straume
  • Lars A. AkslenEmail author


Glomeruloid microvascular proliferations (GMPs), which are focal proliferative buddings of endothelial cells resembling a renal glomerulus, can be induced experimentally by adenoviral transfer of VEGF-A165. We recently found that GMPs were present in 13–23% of various human tumours (melanoma, breast-, endometrial- and prostate cancer), and this vascular signature was significantly associated with an impaired prognosis. In the present study, a series of 202 vertical growth phase melanomas were examined for the expression of various angiogenic factors and their receptors. Presence of GMP was associated with increased expression in tumour endothelium of the VEGF-A receptors KDR, FLT-1 and neuropilin-1, as well as VEGF-D protein. Thrombospondin-1 staining in the tumour stroma showed the same relationship. Endothelial cell expression of VEGF-A was increased in GMP endothelium when compared with other intra-tumoural vessels. In contrast, GMP expression of bFGF was decreased. Our findings suggest an important role of VEGF-A and its receptors in GMP formation in human cutaneous melanoma.

angiogenic factors glomeruloid microvascular proliferation immunohistochemistry melanoma tissue microarray thrombospondin-1 vascular endothelial growth factor 


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Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  1. 1.Department of PathologyThe Gade Institute, Haukeland University HospitalBergenNorway
  2. 2.Department of PathologyThe Gade Institute, Haukeland University HospitalBergenNorway

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