Distinct patterns of chromosomal losses in clinically synchronous and asynchronous bilateral renal cell carcinoma

J Urol. 2002 Dec;168(6):2637-40. doi: 10.1016/S0022-5347(05)64234-6.

Abstract

Purpose: Bilateral renal cell carcinoma has been reported to occur in 1% to 4% of patients with renal cancer. However, whether bilateral renal cell carcinoma involves metastatic lesions of the contralateral kidney or develops as simultaneous primary tumors remains unclear to date. Thus, we investigated chromosomal losses and von Hippel-Lindau (VHL) gene abnormalities in bilateral tumors from patients with nonfamilial bilateral renal cell carcinoma.

Materials and methods: Genomic DNA was exacted from 2 tumors in 8 patients each with nonfamilial bilateral renal cell carcinoma, including clinically asynchronous and synchronous disease in 5 and 3, respectively. The DNA was then subjected to microsatellite analysis on 13 chromosomal loci. In addition, polymerase chain reaction-single nucleotide specific conformation polymorphism analysis and direct sequencing of 3 exons of the VHL gene were performed.

Results: All 5 asynchronous cases showed loss of the same allele in bilateral tumors, indicating a common clonal origin. In contrast, 2 of the 3 synchronous cases showed different patterns of chromosomal loss in the right and left renal tumors, suggesting bilateral primary origins. The other synchronous case with loss of the same allele in each tumor involved right stage T3b and left stage T1a neoplasms. No VHL gene mutations were detected in any case.

Conclusions: Except for a small number of cases synchronous and asynchronous bilateral renal cell carcinoma may represent the simultaneous appearance of separate primary tumors and metastatic progression from the contralateral kidney, respectively.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / secondary
  • Clone Cells
  • DNA, Neoplasm / genetics
  • Female
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Ligases / genetics
  • Loss of Heterozygosity*
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Mutation
  • Neoplasms, Multiple Primary / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Polymorphism, Single-Stranded Conformational
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Von Hippel-Lindau Tumor Suppressor Protein

Substances

  • DNA, Neoplasm
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human