Ok, Chi Young6; Xu-Monette, Zijun Y7; Tzankov, Alexandar7; O'Malley, Dennis P7; Montes-Moreno, Santiago7; Visco, Carlo7; Møller, Michael B7; Dybkær, Karen2; Orazi, Attilio7; Zu, Youli7; Bhagat, Govind7; Richards, Kristy L7; Hsi, Eric D7; Han van Krieken, J7; Ponzoni, Maurilio7; Farnen, John P7; Piris, Miguel A7; Winter, Jane N7; Medeiros, L Jeffrey7; Young, Ken H7
1 The Faculty of Medicine, Aalborg University, VBN2 Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, VBN3 Aalborg University Hospital, The Faculty of Medicine, Aalborg University, VBN4 Klinik Medicin, The Faculty of Medicine, Aalborg University, VBN5 Blodsygdomme (Hæmatologi), The Faculty of Medicine, Aalborg University, VBN6 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.7 unknown
A report from the International DLBCL Rituximab-CHOP Consortium Program
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.