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Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas.
Clin Cancer Res. 2005 Oct 15; 11(20):7226-33.CC

Abstract

PURPOSE

In patients with papillary renal cell carcinoma, it is not uncommon to find two or more anatomically distinct and histologically similar tumors at radical nephrectomy. Whether these multiple papillary lesions result from intrarenal metastasis or arise independently is unknown. Previous studies have shown that multifocal clear cell renal cell carcinomas express identical allelic loss and shift patterns in the different tumors within the same kidney, consistent with a clonal origin. However, similar clonality assays for multifocal papillary renal cell neoplasia have not been done. Molecular analysis of microsatellite and chromosome alterations and X-chromosome inactivation status in separate tumors in the same patient can be used to study the genetic relationships among the coexisting multiple tumors.

EXPERIMENTAL DESIGN

We examined specimens from 21 patients who underwent radical nephrectomy for renal cell carcinoma. All patients had multiple separate papillary lesions (ranging from 2 to 5). Eighteen patients had multiple papillary renal cell carcinomas. Seven had one or more papillary renal cell carcinomas with coexisting papillary adenomas. Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays were done for six microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p14 (D3S1285), 7q31 (D7S522), 9p21 (D9S171), 16q23 (D16S507), 17q21 (D17S1795), and 17p13 (TP53). X-chromosome inactivation analyses were done on the papillary kidney tumors from three female patients. Fluorescence in situ hybridization analysis was done on the tumors of selected patients showing allelic loss at loci on chromosome 7 and/or chromosome 17.

RESULTS

Twenty of 21 (95%) cases showed allelic loss in one or more of the papillary lesions in at least one of the six polymorphic markers analyzed. A concordant allelic loss pattern between each coexisting kidney tumor was seen in only 1 of 21 (5%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the coexisting multiple papillary lesions was seen in two of three female patients. A discordant pattern of X-chromosome inactivation was seen in the tumors of the other female patient. Fluorescence in situ hybridization showed that the majority of tumors analyzed had gains of chromosomes 7 and 17. Two patients had one tumor with chromosomal gain and another separate tumor that did not.

CONCLUSION

Our data suggest that, unlike multifocal clear cell renal cell carcinomas, the multiple tumors in patients with papillary renal cell carcinoma arise independently. Thus, intrarenal metastasis does not seem to play an important role in the spread of papillary renal cell carcinoma, a finding that has surgical, therapeutic, and prognostic implications.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16243792

Citation

Jones, Timothy D., et al. "Molecular Genetic Evidence for the Independent Origin of Multifocal Papillary Tumors in Patients With Papillary Renal Cell Carcinomas." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 20, 2005, pp. 7226-33.
Jones TD, Eble JN, Wang M, et al. Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas. Clin Cancer Res. 2005;11(20):7226-33.
Jones, T. D., Eble, J. N., Wang, M., MacLennan, G. T., Delahunt, B., Brunelli, M., Martignoni, G., Lopez-Beltran, A., Bonsib, S. M., Ulbright, T. M., Zhang, S., Nigro, K., & Cheng, L. (2005). Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(20), 7226-33.
Jones TD, et al. Molecular Genetic Evidence for the Independent Origin of Multifocal Papillary Tumors in Patients With Papillary Renal Cell Carcinomas. Clin Cancer Res. 2005 Oct 15;11(20):7226-33. PubMed PMID: 16243792.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas. AU - Jones,Timothy D, AU - Eble,John N, AU - Wang,Mingsheng, AU - MacLennan,Gregory T, AU - Delahunt,Brett, AU - Brunelli,Matteo, AU - Martignoni,Guido, AU - Lopez-Beltran,Antonio, AU - Bonsib,Stephen M, AU - Ulbright,Thomas M, AU - Zhang,Shaobo, AU - Nigro,Kelly, AU - Cheng,Liang, PY - 2005/10/26/pubmed PY - 2006/2/14/medline PY - 2005/10/26/entrez SP - 7226 EP - 33 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 11 IS - 20 N2 - PURPOSE: In patients with papillary renal cell carcinoma, it is not uncommon to find two or more anatomically distinct and histologically similar tumors at radical nephrectomy. Whether these multiple papillary lesions result from intrarenal metastasis or arise independently is unknown. Previous studies have shown that multifocal clear cell renal cell carcinomas express identical allelic loss and shift patterns in the different tumors within the same kidney, consistent with a clonal origin. However, similar clonality assays for multifocal papillary renal cell neoplasia have not been done. Molecular analysis of microsatellite and chromosome alterations and X-chromosome inactivation status in separate tumors in the same patient can be used to study the genetic relationships among the coexisting multiple tumors. EXPERIMENTAL DESIGN: We examined specimens from 21 patients who underwent radical nephrectomy for renal cell carcinoma. All patients had multiple separate papillary lesions (ranging from 2 to 5). Eighteen patients had multiple papillary renal cell carcinomas. Seven had one or more papillary renal cell carcinomas with coexisting papillary adenomas. Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays were done for six microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p14 (D3S1285), 7q31 (D7S522), 9p21 (D9S171), 16q23 (D16S507), 17q21 (D17S1795), and 17p13 (TP53). X-chromosome inactivation analyses were done on the papillary kidney tumors from three female patients. Fluorescence in situ hybridization analysis was done on the tumors of selected patients showing allelic loss at loci on chromosome 7 and/or chromosome 17. RESULTS: Twenty of 21 (95%) cases showed allelic loss in one or more of the papillary lesions in at least one of the six polymorphic markers analyzed. A concordant allelic loss pattern between each coexisting kidney tumor was seen in only 1 of 21 (5%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the coexisting multiple papillary lesions was seen in two of three female patients. A discordant pattern of X-chromosome inactivation was seen in the tumors of the other female patient. Fluorescence in situ hybridization showed that the majority of tumors analyzed had gains of chromosomes 7 and 17. Two patients had one tumor with chromosomal gain and another separate tumor that did not. CONCLUSION: Our data suggest that, unlike multifocal clear cell renal cell carcinomas, the multiple tumors in patients with papillary renal cell carcinoma arise independently. Thus, intrarenal metastasis does not seem to play an important role in the spread of papillary renal cell carcinoma, a finding that has surgical, therapeutic, and prognostic implications. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/16243792/Molecular_genetic_evidence_for_the_independent_origin_of_multifocal_papillary_tumors_in_patients_with_papillary_renal_cell_carcinomas_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16243792 DB - PRIME DP - Unbound Medicine ER -