CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas: frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma

William R. Sukov, Rhett P. Ketterling, Donna J. Lager, Austin W. Carlson, Jason P. Sinnwell, George K. Chow, Robert Brian Jenkins, John C. Cheville

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Summary: Renal oncocytoma is a benign tumor occurring singly or as multiple synchronous lesions. The histologic features of renal oncocytoma may overlap with those of chromophobe renal cell carcinoma. Chromosomal translocations involving the CCND1 locus at 11q13 and overexpression of cyclin D1 occur in a subset of renal oncocytomas. We evaluated a series of 63 renal oncocytomas and 36 chromophobe renal cell carcinomas and assessed the clinical features, cyclin D1 overexpression by immunohistochemistry, and alterations of the CCND1 gene by fluorescence in situ hybridization. All 36 chromophobe renal cell carcinomas were negative for cyclin D1 overexpression and alterations of CCND1. Of the 63 renal oncocytomas, 21 (33%) showed cyclin D1 overexpression. Of 21 renal oncocytomas with cyclin D1 overexpression, a CCND1 rearrangement was detected in 12 (57%). A CCND1 rearrangement was also identified in 1 (2%) of the 42 renal oncocytomas without cyclin D1 overexpression. Of 42 renal oncocytomas without cyclin D1 overexpression, 16 (38%) were from patients with multiple renal oncocytomas at nephrectomy. Of 21 renal oncocytomas with cyclin D1 overexpression, only 1 (5%) patient had multiple renal oncocytomas (P = .006). Of the 25 patients whose original tumor showed no cyclin D1 overexpression, 8 (32%) developed a subsequent renal oncocytoma. None of 15 patients whose original tumor showed cyclin D1 overexpression had a subsequent renal oncocytoma (P = .016). The findings of this study suggest that renal oncocytomas lacking cyclin D1 overexpression may be associated with the development of multiple renal oncocytomas and that these patients are more likely to develop subsequent renal oncocytomas suggesting the need for more frequent clinical for these patients and little need for follow-up in patients with renal oncocytomas overexpressing cyclin D1. The data also show that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ hybridization are absent in chromophobe renal cell carcinoma, suggesting that these are useful when differentiating between renal oncocytoma and chromophobe renal cell carcinoma.

Original languageEnglish (US)
Pages (from-to)1296-1303
Number of pages8
JournalHuman Pathology
Volume40
Issue number9
DOIs
StatePublished - Sep 2009

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Cyclin D1
Renal Cell Carcinoma
Renal oncocytoma
Fluorescence In Situ Hybridization
Neoplasms
Genetic Translocation

Keywords

  • CCND1
  • Chromophobe renal cell carcinoma
  • Cyclin D1
  • Cytogenetics
  • Renal oncocytoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas : frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma. / Sukov, William R.; Ketterling, Rhett P.; Lager, Donna J.; Carlson, Austin W.; Sinnwell, Jason P.; Chow, George K.; Jenkins, Robert Brian; Cheville, John C.

In: Human Pathology, Vol. 40, No. 9, 09.2009, p. 1296-1303.

Research output: Contribution to journalArticle

Sukov, William R. ; Ketterling, Rhett P. ; Lager, Donna J. ; Carlson, Austin W. ; Sinnwell, Jason P. ; Chow, George K. ; Jenkins, Robert Brian ; Cheville, John C. / CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas : frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma. In: Human Pathology. 2009 ; Vol. 40, No. 9. pp. 1296-1303.
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abstract = "Summary: Renal oncocytoma is a benign tumor occurring singly or as multiple synchronous lesions. The histologic features of renal oncocytoma may overlap with those of chromophobe renal cell carcinoma. Chromosomal translocations involving the CCND1 locus at 11q13 and overexpression of cyclin D1 occur in a subset of renal oncocytomas. We evaluated a series of 63 renal oncocytomas and 36 chromophobe renal cell carcinomas and assessed the clinical features, cyclin D1 overexpression by immunohistochemistry, and alterations of the CCND1 gene by fluorescence in situ hybridization. All 36 chromophobe renal cell carcinomas were negative for cyclin D1 overexpression and alterations of CCND1. Of the 63 renal oncocytomas, 21 (33{\%}) showed cyclin D1 overexpression. Of 21 renal oncocytomas with cyclin D1 overexpression, a CCND1 rearrangement was detected in 12 (57{\%}). A CCND1 rearrangement was also identified in 1 (2{\%}) of the 42 renal oncocytomas without cyclin D1 overexpression. Of 42 renal oncocytomas without cyclin D1 overexpression, 16 (38{\%}) were from patients with multiple renal oncocytomas at nephrectomy. Of 21 renal oncocytomas with cyclin D1 overexpression, only 1 (5{\%}) patient had multiple renal oncocytomas (P = .006). Of the 25 patients whose original tumor showed no cyclin D1 overexpression, 8 (32{\%}) developed a subsequent renal oncocytoma. None of 15 patients whose original tumor showed cyclin D1 overexpression had a subsequent renal oncocytoma (P = .016). The findings of this study suggest that renal oncocytomas lacking cyclin D1 overexpression may be associated with the development of multiple renal oncocytomas and that these patients are more likely to develop subsequent renal oncocytomas suggesting the need for more frequent clinical for these patients and little need for follow-up in patients with renal oncocytomas overexpressing cyclin D1. The data also show that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ hybridization are absent in chromophobe renal cell carcinoma, suggesting that these are useful when differentiating between renal oncocytoma and chromophobe renal cell carcinoma.",
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T2 - frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma

AU - Sukov, William R.

AU - Ketterling, Rhett P.

AU - Lager, Donna J.

AU - Carlson, Austin W.

AU - Sinnwell, Jason P.

AU - Chow, George K.

AU - Jenkins, Robert Brian

AU - Cheville, John C.

PY - 2009/9

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N2 - Summary: Renal oncocytoma is a benign tumor occurring singly or as multiple synchronous lesions. The histologic features of renal oncocytoma may overlap with those of chromophobe renal cell carcinoma. Chromosomal translocations involving the CCND1 locus at 11q13 and overexpression of cyclin D1 occur in a subset of renal oncocytomas. We evaluated a series of 63 renal oncocytomas and 36 chromophobe renal cell carcinomas and assessed the clinical features, cyclin D1 overexpression by immunohistochemistry, and alterations of the CCND1 gene by fluorescence in situ hybridization. All 36 chromophobe renal cell carcinomas were negative for cyclin D1 overexpression and alterations of CCND1. Of the 63 renal oncocytomas, 21 (33%) showed cyclin D1 overexpression. Of 21 renal oncocytomas with cyclin D1 overexpression, a CCND1 rearrangement was detected in 12 (57%). A CCND1 rearrangement was also identified in 1 (2%) of the 42 renal oncocytomas without cyclin D1 overexpression. Of 42 renal oncocytomas without cyclin D1 overexpression, 16 (38%) were from patients with multiple renal oncocytomas at nephrectomy. Of 21 renal oncocytomas with cyclin D1 overexpression, only 1 (5%) patient had multiple renal oncocytomas (P = .006). Of the 25 patients whose original tumor showed no cyclin D1 overexpression, 8 (32%) developed a subsequent renal oncocytoma. None of 15 patients whose original tumor showed cyclin D1 overexpression had a subsequent renal oncocytoma (P = .016). The findings of this study suggest that renal oncocytomas lacking cyclin D1 overexpression may be associated with the development of multiple renal oncocytomas and that these patients are more likely to develop subsequent renal oncocytomas suggesting the need for more frequent clinical for these patients and little need for follow-up in patients with renal oncocytomas overexpressing cyclin D1. The data also show that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ hybridization are absent in chromophobe renal cell carcinoma, suggesting that these are useful when differentiating between renal oncocytoma and chromophobe renal cell carcinoma.

AB - Summary: Renal oncocytoma is a benign tumor occurring singly or as multiple synchronous lesions. The histologic features of renal oncocytoma may overlap with those of chromophobe renal cell carcinoma. Chromosomal translocations involving the CCND1 locus at 11q13 and overexpression of cyclin D1 occur in a subset of renal oncocytomas. We evaluated a series of 63 renal oncocytomas and 36 chromophobe renal cell carcinomas and assessed the clinical features, cyclin D1 overexpression by immunohistochemistry, and alterations of the CCND1 gene by fluorescence in situ hybridization. All 36 chromophobe renal cell carcinomas were negative for cyclin D1 overexpression and alterations of CCND1. Of the 63 renal oncocytomas, 21 (33%) showed cyclin D1 overexpression. Of 21 renal oncocytomas with cyclin D1 overexpression, a CCND1 rearrangement was detected in 12 (57%). A CCND1 rearrangement was also identified in 1 (2%) of the 42 renal oncocytomas without cyclin D1 overexpression. Of 42 renal oncocytomas without cyclin D1 overexpression, 16 (38%) were from patients with multiple renal oncocytomas at nephrectomy. Of 21 renal oncocytomas with cyclin D1 overexpression, only 1 (5%) patient had multiple renal oncocytomas (P = .006). Of the 25 patients whose original tumor showed no cyclin D1 overexpression, 8 (32%) developed a subsequent renal oncocytoma. None of 15 patients whose original tumor showed cyclin D1 overexpression had a subsequent renal oncocytoma (P = .016). The findings of this study suggest that renal oncocytomas lacking cyclin D1 overexpression may be associated with the development of multiple renal oncocytomas and that these patients are more likely to develop subsequent renal oncocytomas suggesting the need for more frequent clinical for these patients and little need for follow-up in patients with renal oncocytomas overexpressing cyclin D1. The data also show that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ hybridization are absent in chromophobe renal cell carcinoma, suggesting that these are useful when differentiating between renal oncocytoma and chromophobe renal cell carcinoma.

KW - CCND1

KW - Chromophobe renal cell carcinoma

KW - Cyclin D1

KW - Cytogenetics

KW - Renal oncocytoma

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