Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas

Timothy D. Jones, John Eble, Mingsheng Wang, Gregory T. MacLennan, Brett Delahunt, Matteo Brunelli, Guido Martignoni, Antonio Lopez-Beltran, Stephen M. Bonsib, Thomas Ulbright, Shaobo Zhang, Kelly Nigro, Liang Cheng

Research output: Contribution to journalArticle

82 Citations (Scopus)

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 analysts 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 (D9ST71), 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.

Original languageEnglish
Pages (from-to)7226-7233
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number20
DOIs
StatePublished - Oct 15 2005

Fingerprint

Renal Cell Carcinoma
Molecular Biology
Loss of Heterozygosity
Neoplasms
X Chromosome Inactivation
Kidney
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 7
Nephrectomy
Fluorescence In Situ Hybridization
Microsatellite Repeats
Chromosomes
Neoplasm Metastasis
Laser Capture Microdissection
Tumor Suppressor Genes
Adenoma
Paraffin
Formaldehyde
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas. / Jones, Timothy D.; Eble, John; Wang, Mingsheng; MacLennan, Gregory T.; Delahunt, Brett; Brunelli, Matteo; Martignoni, Guido; Lopez-Beltran, Antonio; Bonsib, Stephen M.; Ulbright, Thomas; Zhang, Shaobo; Nigro, Kelly; Cheng, Liang.

In: Clinical Cancer Research, Vol. 11, No. 20, 15.10.2005, p. 7226-7233.

Research output: Contribution to journalArticle

Jones, Timothy D. ; Eble, John ; Wang, Mingsheng ; MacLennan, Gregory T. ; Delahunt, Brett ; Brunelli, Matteo ; Martignoni, Guido ; Lopez-Beltran, Antonio ; Bonsib, Stephen M. ; Ulbright, Thomas ; Zhang, Shaobo ; Nigro, Kelly ; Cheng, Liang. / Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 20. pp. 7226-7233.
@article{24f92917a1724e30973ea82dcde4ae84,
title = "Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas",
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 analysts 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 (D9ST71), 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.",
author = "Jones, {Timothy D.} and John Eble and Mingsheng Wang and MacLennan, {Gregory T.} and Brett Delahunt and Matteo Brunelli and Guido Martignoni and Antonio Lopez-Beltran and Bonsib, {Stephen M.} and Thomas Ulbright and Shaobo Zhang and Kelly Nigro and Liang Cheng",
year = "2005",
month = "10",
day = "15",
doi = "10.1158/1078-0432.CCR-04-2597",
language = "English",
volume = "11",
pages = "7226--7233",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "20",

}

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

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

AU - Zhang, Shaobo

AU - Nigro, Kelly

AU - Cheng, Liang

PY - 2005/10/15

Y1 - 2005/10/15

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 analysts 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 (D9ST71), 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.

AB - 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 analysts 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 (D9ST71), 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.

UR - http://www.scopus.com/inward/record.url?scp=27144456179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27144456179&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-04-2597

DO - 10.1158/1078-0432.CCR-04-2597

M3 - Article

C2 - 16243792

AN - SCOPUS:27144456179

VL - 11

SP - 7226

EP - 7233

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 20

ER -