Expression of hepatocyte growth factor and its receptor C-met in acquired renal cystic disease associated with renal cell carcinoma.
OBJECTIVE
The development of renal cell carcinoma (RCC) is a critical problem in acquired renal cystic disease (ARCD) in patients with end stage renal disease, particularly males on chronic hemodialysis. We examined the expression of hepatcyte growth factor (HGF) and its receptor c-met in ARCD associated with RCC to elucidate the role of the HGF/c-met pathway in renal cyst development and subsequent tumor transformation.


METHODS
Immunohistochemical expression of HGF, c-met and Bcl-2 was examined in 15 normal tissue samples of kidneys obtained from nephrectomy for localized RCC and 19 with ARCD associated with RCC from 16 patients on dialysis. The expression of HGF mRNA was examined by reverse transcriptase-polymerase chain reaction.


RESULTS
In normal kidneys immunostaining for HGF was scarcely detected in renal tubular cells. Bcl-2 and c-met immunostaining was observed mainly in distal tubular cells. In nontumor areas of kidneys with ARCD associated RCC the expression of HGF and c-met was up-regulated in tubular and the cyst epithelial cells. Hyperplastic cysts with multilayer epithelium and micropapillary projection were the predominant cysts stained with HGF and c-met. Immunostaining for HGF and c-met was also detected in RCC regions. The Bcl-2 immunostaining pattern was similar to that of HGF and c-met in nontumor and RCC regions. On reverse transcriptase-polymerase chain reaction HGF mRNA expression was up-regulated in nontumor areas and RCC regions in ARCD.


CONCLUSIONS
These results suggest that up-regulation of HGF and its receptor c-met may be involved in renal cyst formation and subsequent tumor transformation in patients with end stage renal disease. Increased Bcl-2 expression may promote this process through the inhibition of apoptosis.
Konda
Ryuichiro
R
Department of Urology, Iwate Medical University School of Medicine, Morioka, Japan. Ryukonda@iwate-med.ac.jp
Sato
Hiroshi
H
Hatafuku
Fumihiko
F
Nozawa
Tatsuru
T
Ioritani
Naomasa
N
Fujioka
Tomoaki
T
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000150:complications* / Q000378:metabolism*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D052177:Kidney Diseases, Cystic / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000150:complications*; D007680:Kidney Neoplasms / Q000150:complications* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met