Different vascular endothelial growth factor (VEGF), VEGF-receptor 1 and -2 mRNA expression profiles between clear cell and papillary renal cell carcinoma.
OBJECTIVE
To examine vascular endothelial growth factor (VEGF), VEGF-receptor-(R)1, and R2 mRNA levels in renal cell carcinoma (RCC), a tumour generally refractory to most medical therapy, but for which a potentially useful therapeutic alternative is inhibition of angiogenesis.


METHODS
VEGF, VEGF-R1 and -R2 mRNA levels were analysed using the quantitative reverse transcription-polymerase chain reaction. RNA was extracted from 84 conventional (clear cell) RCCs (cRCC), 20 papillary (pRCC), six chromophobe (chRCC), and 27 corresponding kidney cortex tissues, obtained from 110 patients in whom high-quality RNA was available from the tumours (53 women and 57 men, mean age 64.7 years, range 25-85).


RESULTS
The VEGF, VEGF-R1, and -R2 mRNA levels were higher in tumour than in kidney cortex tissues. Among the RCC types, cRCC had higher VEGF levels than pRCC. In cRCC, VEGF-R2 levels were higher in stage I-II than in more advanced stages. In pRCC, VEGF and VEGF-R2 levels were higher in stage III than in stage I-II tumours. In cRCC, patients with VEGF levels below the median had a significantly shorter survival time than those with higher levels. By contrast, in pRCC, VEGF, VEGF-R1 and -R2 RNA levels above the median were related to adverse survival. Using multivariate analysis in cRCCs, VEGF-R1 mRNA level was the last factor to be omitted after stepwise elimination analysis.


CONCLUSIONS
VEGF and its receptors were associated with tumour stage and survival, but were not independent prognostic factors. Different RCC types had different expression patterns of VEGF and receptor mRNA levels. We conclude that different pathways might be involved in regulating angiogenesis in the specific RCC types. Detailed knowledge of angiogenesis in RCC is essential when designing new treatment trials where angiogenesis inhibition is used.
Ljungberg
Börje J
BJ
Urology and Andrology, Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden. borje.ljungberg@urologi.umu.se
Jacobsen
Jan
J
Rudolfsson
Stina Häggström
SH
Lindh
Gudrun
G
Grankvist
Kjell
K
Rasmuson
Torgny
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
D012333:RNA, Messenger; D042442:Vascular Endothelial Growth Factors; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2