PB2108: PREVALENCE AND CLINICAL IMPLICATIONS OF CYCLIN D1 POSITIVE DIFFUSE LARGE B-CELL LYMPHOMA IN CHINA

Abstract

Background: Cyclin D1 protein expression in lymphocytes is classically associated with mantle cell lymphoma. It has been ralely reported in patients with diffuse large B-cell leukemia (DLBCL), and studies have been few and generally small, and they were no obvious clinical implications attributable to cyclin D1 expression in China. Aims: To investigate clinical implications attributable to cyclin D1 expression n patients with diffuse large B-cell leukemia (DLBCL) in China. Methods: he authors reviewed 541 patients who were diagnosed with DLBCL treated with R-CHOP (rituximab with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone,R-CHOP) in 3 years. 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. Clinical and immunohistochemical features were performed to compare patients who had DLBCL with and without cyclin D1 expression. Results: In total, 11 patients (2.0%) who had DLBCL that expressed cyclin D1 and lacked CCND1 gene rearrangements. Patients with cyclin D1-positive DLBCL had a median age of 59.45±3.10 years (ranged 48-80 years). There were 7 males and 4 females. B-symptoms were present in 18.2% of patients. 90.9% patients were regarded as IV stage. The International Prognostic Index was high-intermediate and high (>3) in 81.8% of patients. Two or more extranodal sites were involved in 36.4% of patients. CD20 was positive in all cases. These cases showed a strong nuclear positivity for cyclin D1 in the DLBCL, but no expression of CD5 and SOX11 was detected. All cases were consistently negative for CD10, BCL6 was positive in 8 of 11 cases (72.2%), and MUM1 was positive in 9/11 cases (81.8%). The majority of cases (90.9%) showed expression of MYC. All cases showed a proliferation rate above 80%. Patients with cyclin D1-positive DLBCL patients had more Ki-67 proliferation, elevated serum lactate dehydrogenase and more advanced stage (P<.05). The other clinical characteristics, such as sex, age, extraodal site, IPI score, and β macroglobulin level did not differ significantly (P>.05). However, patients with cyclin D1-positive DLBCL had shorter PFS and OS than cyclin D1-negative patients (P<0.05). Cyclin D1-positive DLBCL patients with MYC or MYC/BCL2 coexpression showed poorer prognosis than double protein lymphoma (DPL) patients, but did not significantly (P>.05). Summary/Conclusion: Compared with patients who had cyclin D1-negative DLBCL, cyclin D1-positive DLBCL patients had later staging and greater tumor load with more Ki-67 proliferation. There were no other significant differences in clinical presentation, pathologic features. Cyclin D1-positive DLBCL patients showed poorer overall survival and progression-free survival than cyclin D1-negative patients.