Evidence for Polyclonal Origin of Multifocal Clear Cell Renal Cell Carcinoma
L Cheng, GT MacLennan, S Zhang, M Wang, M Zhou, PH Tan, JM Kehoe, CL Meshberger, A Lopez-Beltran, R Montironi. Indiana University, Indianapolis; Case Western Reserve University, Cleveland; Cleveland Clinic, Cleveland; Singapore General Hospital, Singapore, Singapore; Cordoba University, Cordoba, Spain; Polytechnic University of the Marche Region (Ancona) and United Hospitals, Ancona
Background: With the increased use of nephron sparing surgical excision of renal neoplasms, concern has been expressed that limited surgical resections may not encompass multifocal renal cell tumors, specifically those that are too small to be visualized radiologically, with the result that such unresected tumors would ultimately require additional treatment. Consequently, a clear understanding of the genetic relationships between multifocal renal tumors in the same patient and a reasonably accurate knowledge of the malignant potential of each lesion could have important diagnostic, therapeutic, and prognostic implications.
Design: A total of 62 tumors from 26 patients who underwent radical nephrectomy were examined. All patients had multiple separate clear cell renal carcinomas. Loss of heterozygosity analyses were performed using five microsatellite polymorphic markers that represent putative tumor suppressor genes on chromosome 3p14 (D3S1300), 7q31 (D7S522), 8p22 (D8S261), 9p21 (D9S171) and 17p13 (TP53). X-chromosome inactivation analyses were also performed on the renal tumors from the 10 female patients. Chromosome 3p deletion status was determined by dual color interphase fluorescence in situ hybridization analysis in all tumors.
Results: Nineteen of the 26 (73%) patients with multifocal clear cell renal cell carcinoma showed allelic loss in at least one of five microsatellite loci in separate tumors analyzed. A disconcordant pattern of allelic loss between coexisting kidney tumors was observed in 7 cases. Six cases showed discordant 3p deletion patterns by dual color interphase fluorescence in situ hybridization analysis. Of the eight informative female cases studied by X-chromosome inactivation, one showed a discordant non-random pattern of X-chromosome inactivation. Overall, evidence of independent origin of the multifocal renal tumors was observed in 12 of 26 cases (46%).
Conclusions: Our data suggest that in a significant number of cases of multifocal clear cell renal cell carcinoma, the spatially separate tumors are of different clonal origin and arise independently.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 104, Tuesday Morning