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Clonal origin of multifocal renal cell carcinoma as determined by microsatellite analysis
Kerstin Junker1, Katharina Thrum, Andreas Schlichter
1Department of Urology, Institute of Pathology, Friedrich-Schiller-University, Jena, Germany.
Purpose:
The reported incidence of satellite tumor lesions in renal cell carcinoma (7% to 25%) suggests that there is a risk of local recurrence after nephron sparing surgery. It remains largely unknown whether small satellite tumors show malignant features and whether they are metastases from the primary tumor. Therefore, we determined the clonality of multifocal tumors by molecular genetic analysis.
Materials And Methods:
A total of 19 multifocal clear cell renal cell carcinomas were investigated by microsatellite analysis using 6 markers for chromosome 3p, namely D3S1560, D3S1289, D3S1766, D3S1300, D3S1566 and D3S1663. Polymerase chain reaction was performed according to standard protocols, followed by gel electrophoresis and automated analysis using an automated DNA sequencer (Li-Cor, Lincoln, Nebraska).
Results:
All primary clear cell tumors were characterized by loss of heterozygosity on 3p. Multifocal tumors showed identical microsatellite alterations with at least 1 marker in 17 of the 19 cases. In 2 cases different microsatellite patterns were detected in tumors from the same kidney.
Conclusions:
Identical loss of heterozygosity and shift patterns detected in different tumors in the same kidney strongly suggest that multifocal clear cell renal cell carcinomas have a common clonal origin in most cases. These findings indicate that satellite tumors are the result of intrarenal metastasis from the primary tumor. The clinical implications of these results must be correlated with the clinical disease course in patients with multifocal renal cell carcinoma.
Insights
Multifocal renal cell carcinomas often share a common origin, suggesting satellite tumors are intrarenal metastases. This finding impacts understanding local recurrence risk after kidney-sparing surgery.
Area of Science:
- Oncology
- Molecular Genetics
- Uropathology
Background:
- Satellite lesions in renal cell carcinoma (RCC) occur in 7-25% of cases, posing a risk for local recurrence after nephron-sparing surgery.
- The malignant potential and metastatic origin of these small satellite tumors remain largely uncharacterized.
Purpose of the Study:
- To determine the clonal origin of multifocal tumors in clear cell renal cell carcinoma (ccRCC) using molecular genetic analysis.
- To investigate whether satellite tumors represent intrarenal metastases.
Main Methods:
- Microsatellite analysis was performed on 19 multifocal ccRCC samples using 6 chromosome 3p markers.
- Standard polymerase chain reaction, gel electrophoresis, and automated DNA sequencing were employed.
Main Results:
- All primary ccRCC tumors exhibited loss of heterozygosity on chromosome 3p.
- Seventeen of 19 cases showed identical microsatellite alterations in multifocal tumors, indicating a common clonal origin.
- Two cases displayed distinct microsatellite patterns within the same kidney.
Conclusions:
- Identical microsatellite alterations in multifocal ccRCC strongly suggest a common clonal origin in most instances.
- These findings support the hypothesis that satellite tumors in ccRCC are a result of intrarenal metastasis.
- Further correlation with clinical outcomes is necessary to understand the implications for patients with multifocal RCC.