Prevalence and clinical implications of cyclin D1 expression in diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy: A report from the International DLBCL Rituximab-CHOP Consortium Program

Chi Young Ok, Zijun Y. Xu-Monette, Alexandar Tzankov, Dennis P. O'Malley, Santiago Montes-Moreno, Carlo Visco, Michael B. Møller, Karen Dybkær, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, J. Han Van Krieken, Maurilio Ponzoni, John P. Farnen, Miguel A. Piris, Jane N. Winter, L. Jeffrey Medeiros, Ken H. Young*

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

BACKGROUND Cyclin D1 expression has been reported in a subset of patients with diffuse large B-cell leukemia (DLBCL), but studies have been few and generally small, and they have demonstrated no obvious clinical implications attributable to cyclin D1 expression. METHODS The authors reviewed 1435 patients who were diagnosed with DLBCL as part of the International DLBCL rituximab with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) Consortium Program and performed clinical, immunohistochemical, and genetic analyses with a focus on cyclin D1. All patients who were cyclin D1-positive according to immunohistochemistry were also assessed for rearrangements of the cyclin D1 gene (CCND1) using fluorescence in situ hybridization. Gene expression profiling was performed to compare patients who had DLBCL with and without cyclin D1 expression. RESULTS In total, 30 patients (2.1%) who had DLBCL that expressed cyclin D1 and lacked CCND1 gene rearrangements were identified. Patients with cyclin D1-positive DLBCL had a median age of 57 years (range, 16.0-82.6 years). There were 23 males and 7 females. Twelve patients (40%) had bulky disease. None of them expressed CD5. Two patients expressed cyclin D2. Gene expression profiling indicated that 17 tumors were of the germinal center type, and 13 were of the activated B-cell type. Genetic aberrations of B-cell leukemia/lymphoma 2 (BCL2), BCL6, v-myc avian myelocytomatosis viral oncogene homolog (MYC), mouse double minute 2 oncogene E3 ubiquitin protein ligase (MDM2), MDM4, and tumor protein 53 (TP53) were rare or absent. Gene expression profiling did not reveal any striking differences with respect to cyclin D1 in DLBCL. CONCLUSIONS Compared with patients who had cyclin D1-negative DLBCL, men were more commonly affected with cyclin D1-positive DLBCL, and they were significantly younger. There were no other significant differences in clinical presentation, pathologic features, overall survival, or progression-free survival between these two subgroups of patients with DLBCL.

Original languageEnglish (US)
Pages (from-to)1818-1829
Number of pages12
JournalCancer
Volume120
Issue number12
DOIs
StatePublished - Jun 15 2014

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Keywords

  • cyclin D1
  • diffuse large B-cell lymphoma
  • pleomorphic mantle cell lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ok, C. Y., Xu-Monette, Z. Y., Tzankov, A., O'Malley, D. P., Montes-Moreno, S., Visco, C., Møller, M. B., Dybkær, K., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Han Van Krieken, J., Ponzoni, M., Farnen, J. P., Piris, M. A., Winter, J. N., Medeiros, L. J., & Young, K. H. (2014). Prevalence and clinical implications of cyclin D1 expression in diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy: A report from the International DLBCL Rituximab-CHOP Consortium Program. Cancer, 120(12), 1818-1829. https://doi.org/10.1002/cncr.28664