Characterization of D-cyclin proteins in hematolymphoid neoplasms: Lack of specificity of cyclin-D2 and D3 expression in lymphoma subtypes

Ryan A. Metcalf, Shuchun Zhao, Matthew W. Anderson, Zhi Shun Lu, Ilana Galperin, Robert J. Marinelli, Athena M. Cherry, Izidore S. Lossos, Yasodha Natkunam

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

D-cyclin proteins play a central role in cell-cycle regulation and are involved in the pathogenesis of lymphomas. In mantle-cell lymphoma, the t(11;14) translocation leads to overexpression of cyclin-D1, in addition to which cyclin-D1-negative mantle-cell lymphoma that overexpress cyclin-D2 or D3 have also been described. Although cyclin-D2 and D3 have been implicated in the prognosis of specific lymphoma subtypes, a thorough characterization of D-cyclin protein expression in human hematolymphoid neoplasia has not been reported. To evaluate the tissue expression patterns of D-cyclins, particularly D2 and D3, in normal and neoplastic hematolymphoid tissues, we optimized the commercially available antibodies for D-cyclins for use on paraffin-embedded tissue and stained tissue microarrays of over 700 patient samples. Our results show that cyclin-D2 and D3 proteins are expressed in many more lymphoma subtypes than cyclin-D1. Cyclin-D1, D2 and D3 were expressed in 100, 22 and 6% of mantle-cell lymphomas and 2, 49 and 20% of diffuse large B-cell lymphomas. Fluorescence in situ hybridization studies confirmed the presence of the CCND1/IGH translocation in the majority of mantle-cell lymphoma, but not in diffuse large B-cell lymphoma that expressed cyclin-D1 protein. In addition, a subset of follicular, marginal zone, lymphoplasmacytic, lymphoblastic, classical Hodgkin, mature T-cell and natural killer cell lymphomas and acute myeloid leukemias also expressed cyclin-D2 and D3. These data support the hypothesis that dysregulation of cell-cycle control by D-cyclins contribute to the pathogenesis of hematolymphoid neoplasia, and suggest a potential role for these proteins in the prognostic and therapeutic aspects of these diseases. For diagnostic purposes, however, the expression of D-cyclin proteins should be interpreted with caution in the subclassification of lymphoma types.

Original languageEnglish (US)
Pages (from-to)420-433
Number of pages14
JournalModern Pathology
Volume23
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • CCND2
  • CCND3
  • Cyclin-D2
  • Cyclin-D3
  • Diffuse large B-cell lymphoma
  • Tissue microarray

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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