Different angiogenic potential in low and high grade sporadic clear cell renal cell carcinoma is not related to alterations in the von Hippel-Lindau gene.
BACKGROUND
von Hippel-Lindau (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.


CONCLUSIONS
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.
Baldewijns
Marcella M
MM
Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. m.baldewijns@mumc.nl
van Vlodrop
Iris J H
IJ
Smits
Kim M
KM
Vermeulen
Peter B
PB
Van den Eynden
Gert G
GG
Schot
Fiona
F
Roskams
Tania
T
van Poppel
Hein
H
van Engeland
Manon
M
de Bruïne
Adriaan P
AP
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism
D051794:Von Hippel-Lindau Tumor Suppressor Protein