ABSTRACT
Objective@#To investigate the strong expression (S+) of P53 and BCL2 proteins in MYC/BCL2 double-expression DLBCL (DEL) and whether they can be used for the prognostic evaluation and stratified diagnosis of DELs.@*Methods@#Tissue microarray were made by filed FFPE blocks of 174 DLBCL cases. The translocation of MYC, BCL2 and BCL6 genes were detected by FISH, and the proteins were detected by IHC. Data of clinicopathologic features and follow up of patients were collected and OS (overall survival) and PFS (progression free survival) were analyzed by statistics.@*Results@#Eight double-hit lymphomas (DHLs) were identified in all cases, and 45 DELs were selected from 166 remaining cases, which have no significant difference in OS and PFS compared with non-DEL cases (P=0.668 and P=0.790) . Of 42 DEL-cases with follow up data, 24 cases with P53+ or/and BCL2 (S+) are significantly shorter OS and PFS than others (P=0.003 and P=0.000) , in which the cases with P53+/BCL2 (S+) co-expression were the worst prognosis, and P53/BCL2 co-weaker positive DEL cases even have superior OS and PFS than those non-DELs. Although statistics showed that the cases of P53+ or/and BCL2 (S+) have a lower OS and PFS in total cases (P=0.063 and P=0.024) , it is not the case when the DEL-cases take out from total cases, that is the cases with P53+ or/and BCL2 (S+) are as similar OS and PFS as others in non-DEL group (P=0.590 and P=0.550) .@*Conclusion@#The strong expression of P53 and BCL2 proteins can be used as indicators of stratified diagnosis and poor prognosis of DEL.
ABSTRACT
Objective To evaluate the efficacy, safety and the prognosis of rituximab combined with CHOP (R-CHOP) or combined with EPOCH (R-EPOCH) regimen in treatment of newly diagnosed myc/bcl-2 double-expression diffuse large B-cell lymphoma (DLBCL). Methods The clinical efficacy, adverse reactions and survival of 16 DLBCL patients who received R-CHOP regimen with double-expression and 15 DLBCL patients who received R-EPOCH regimen with double-expression between August 2014 and December 2017 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed, and all patients with double or triple-hit lymphoma were excluded. Results The ratio of the International Prognostic Index (IPI) score ≥3 in R-EPOCH group was higher than that in R-CHOP group [10 cases vs. 5 cases, χ2＝ 3.888, P＝0.049]. There were no statistical differences in other clinical data of both groups. Complete remission (CR) was achieved in 75% (12/16) of R-CHOP group and 67% (10/15) of R-EPOCH group, and there was no statistical difference between the two groups (χ2＝ 0.013, P＝ 0.908). The incidence of grade 3-4 leukopenia and grade 3-4 thrombocytopenia in R-EPOCH group was higher than that in R-CHOP group, and the difference was statistically significant [93% (14/15) vs. 38% (6/16), χ 2＝ 10.542, P＝ 0.01; 73% (11/15) vs. 6% (1/16), χ 2＝ 14.685, P< 0.01]. The 1-year overall survival (OS) rate and progression-free survival (PFS) rate was 86.5% and 81.3% in R-CHOP group, 76.0% and 51.4% in R-EPOCH group. There was no statistical difference in the 1-year OS rate between the two groups (P＞0.05), and the 1-year PFS rate in R-CHOP group was higher than that in R-EPOCH group (P<0.01). The 1-year OS rate and PFS rate was 100.0% and 93.8% in IPI<3 group, 65.5% and 45.0% in IPI≥3 group. The 1-year OS rate and PFS rate in IPI<3 group were superior to those in IPI≥3 group (all P ＞0.01). The 1-year OS rate and PFS rate of the female group were lower than those of the male group (59.6% vs. 100.0%, 44.2% vs. 86.3%), and there were statistical differences (all P<0.01). Cox regression analysis showed that high IPI score was an independent prognostic factor for all patients ( HR＝6.335, 95% CI 0.740-54.261, P＝0.092). Conclusions R-EPOCH and R-CHOP are the ideal treatment methods for the double-expression lymphoma. Both regimens have similarities in the treatment outcome of myc/bcl-2 double-expression DLBCL. The adverse reactions in R-EPOCH group are severer than those in R-CHOP group.
ABSTRACT
Objective To study the frequency of diffuse large B-cell lymphoma (DLBCL) with multi-genetic alteration, and its correlation with c-myc, bcl-2 and bcl-6 protein expression. Methods 50 cases diagnosed with DLBCL from January 2012 to December 2016 were collected. The expression of c-myc, bcl-2 and bcl-6 was analyzed by immunohistochemistry. Interphase fluorescence in situ hybridization (I-FISH) analysis was performed to identify the genetic alteration of c-myc, bcl-2 and bcl-6. Results In all cases, there were 27 males and 23 females with a median age of 50 years (range: 3-85 years). 23 (46.00 %) cases were defined as primary nodal DLBCL and 27 (54.00 %) cases were primary extra-nodal DLBCL, with gastrointestinal tract (48.15 %, 13/27) being the most common site of involvement. c-myc protein expression was detected in 94.00 % (47/50) cases, in which 82.00 % (41/47) cases exhibited high levels of c-myc expression with positive nuclear staining observed in over 40.00 % of tumor cells. The positive rate of bcl-2 protein was 84.00 % (42/50), 76 % (38/50) cases presented with high-level bcl-2 expression. Concurrent high expression of c-myc and bcl-2 were presented in 18 cases (36.00%). FISH analysis demonstrated c-myc gene rearrangement in 7 cases (14.00 %) and amplification in 2 cases (4.00 %). bcl-2 gene rearrangement was detected in 6 cases (12.00 %) and 4 cases (8.00 %) exhibited gene amplification. bcl-6 gene rearrangement was identified in 8 cases (16.00%), amplification in 3 cases (6.00%), and 1 case concomitantly harbored the rearrangement and amplification of bcl-6. Multi-genetic alterations were defined in 4 cases with 3 cases fulfilling the criteria for double-hit lymphoma (DHL) and 1 case for triple-hit lymphoma (THL). For the cases with concomitant high-level expression of c-myc and bcl-2 proteins, 3 cases (16.67 %) was detected with multi-genetic alterations, including 2 cases for DHL and 1 case for THL. Conclusions The proportion of DLBCL with multi-genetic alterations is 8.00 % in this study. The genetic alterations are not consistently correlated with the protein expression. The molecular genetic testing is reliable for the identification of DHL.