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No association was found between BCL6 rearrangement and either BCL6 or BCL2 protein expression. No relationship between BCL6 rearrangement and a high Ki-67 proliferation index was observed. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases: concurrent BCL2/MYC rearrangement in 4 cases and BCL6/MYC in 2 cases. An additional case had rearrangements involving all 3 genes (BCL2/BCL6/MYC). Double-hit or triple-hit lymphoma patients included 4 females and 3 males with a median age of 49 years (range, 17-68). No patient had a prior diagnosis of lymphoma at the time of clinical presentation. Four Nutlin3a cases had primary extranodal and 3 primary nodal presentations. The majority of patients had stage III or IV disease (6 of 7, 86%) and high-risk IPI scores (6 of 7, 86%). Bone marrow selleck chemicals llc involvement was present in 1 patient (1 of 7, 14%) and central nervous system involvement in 1 patient (1 of 7, 14%). The morphology and immunophenotype of the tumor cells was consistent with DLBCL, not otherwise specified (NOS) in 6 cases and B-cell lymphoma, unclassifiable in 1 case, according to the 2008 WHO classification. One case had coexisting follicular lymphoma grade 3B and DLBCL at diagnosis. BCL2 protein expression was found in 6 (86%) of 7 cases. The majority of cases (5 of 7, 71%) had a GC phenotype, whereas 2 cases had a non-GC phenotype. The majority of these cases (6 of 7, 86%) had a high proliferation rate (Ki-67 ��80%). Morphological features consistent with DLBCL-NOS and rearrangements of MYC, BCL2, and BCL6 are shown in the case of triple-hit lymphoma in Figure 2. We studied clinicopathological characteristics and their association with PFS and OS by univariate analysis for 145 R-CHOP�Ctreated patients (Table 2). Among clinical parameters, an IPI score >2 (high-risk IPI) was associated with worse OS (P < .001), as was advanced stage (stage III or IV, P = .03). By univariate analysis, CD10, BCL6, MUM1/IRF4, and BCL2 expressions and high proliferation rate were not prognostic Romidepsin for PFS or OS. Similarly, no significant difference in PFS (P = .1) or OS (P = .3) was observed between the GC and non-GC phenotypes. Considering FISH analysis, patients with MYC gene rearrangements had significantly worse OS (P = .01; Fig. 3A) than those without MYC rearrangement, but not PFS (P = .1). In particular, when analyzed according to GC and non-GC phenotypes, the prognostic implication of MYC rearrangement was statistically significant only for the GC phenotype, in which patients with MYC rearrangement had significantly shorter OS (P = .009) and tended to have worse PFS (P = .09). However, no significant prognostic impact of MYC rearrangement on PFS (P = .6) or OS (P = .1) was observed for the patients with non-GC phenotype. BCL6 rearrangement had a significantly unfavorable impact on OS (P = .04; Fig.
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