Genetic identification of bilateral primary or metastatic nonpapillary renal cell carcinoma.
OBJECTIVE
To clarify the clonality of bilateral tumours by genetic analysis of bilateral renal cell carcinomas (RCCs) using the VHL gene, which is inactivated in approximately 60% of RCCs and which plays a causal role in the development of most cases of nonpapillary RCC.


METHODS
The study included 20 patients; seven had von Hippel-Lindau disease, three had papillary RCC and 10 had nonpapillary RCC. Paraffin-embedded blocks of tumour tissue were obtained from two of the three patients with papillary RCC and from nine of 10 with nonpapillary disease; all three exons of VHL were examined by direct sequencing.


RESULTS
As reported previously, no VHL mutations were found in papillary tumours. However, in five of the nine nonpapillary cases, VHL mutations were identified in tumours on one or both sides. Three of the tumours had the same mutation on both sides, confirming a common origin. In the remaining two patients, the mutation status differed between the sides, confirming a bilateral primary origin. The former cases were characterized by a relatively large tumour on one side and multiple tumours on the other.


CONCLUSIONS
In nonpapillary RCC multiplicity may suggest a metastatic origin. Such genetic information will be useful in treating and following patients with bilateral renal tumours.
Departments of Urology and Molecular Pathology, Faculty of Medicine, University of Tokyo, Japan. hyykume@gol.com
H
H
Kume
H
H
Oda
Y
Y
Nakatsuru
Y
Y
Shimizu
Y
Y
Takahashi
T
T
Matsumoto
T
T
Inoue
S
S
Kameyama
T
T
Kitamura
T
T
Ishikawa
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008025:Ligases; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D004273:DNA, Neoplasm; D011506:Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human