Title
Different angiogenic potential in low and high grade sporadic clear cell renal cell carcinoma is not related to alterations in the von HippelLindau gene
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Subject
Human medicine
Source (journal)
Cellular oncology
Volume/pages
31(2009) :5 , p. 371-382
ISSN
1570-5870
ISI
000270463400005
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background: von HippelLindau (VHL) inactivation is common in sporadic clear cell renal cell carcinomas (ccRCC). pVHL is part of the ubiquitin ligase complex that targets the alpha subunits of hypoxia-inducible transcription factor (HIF) for degradation under well-oxygenated conditions. In the absence of wild-type pVHL, as observed in VHL patients and most sporadic ccRCCs, constitutive upregulation of HIF results in transcriptional activation of angiogenesis-related genes, such as VEGF. Differences in angiogenic activity within the group of ccRCCs were reported and strong genotype-phenotype correlations were found in patients with VHL disease, raising a question about the importance of VHL inactivation status in angiogenic behaviour and tumour progression. Methods: To address this question, we investigated the influence of VHL mutation (direct sequencing)/hypermethylation (methylation-specific PCR) on angiogenesis/tumour parameters (immunohistochemistry) in 150 patients with sporadic ccRCC. Results: We found no significant association between VHL mutation or methylation and angiogenesis/tumour parameters. Conclusion: These data indicate that tumour progression and angiogenesis are not directly influenced by VHL alterations and that additional genetic/epigenetic events should be considered to explain the diverse angiogenic and proliferative behaviour during tumour progression.
E-info
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