METHODS: Using a panel of antibodies to CD10, Bcl-6, MUM1 and CD138, consecutive cases of primary UAT DLBCL were stratified into subgroups of germinal centre B-cell-like (GCB) and non-GCB, phenotype profile patterns A, B and C, as proposed by Hans et al. and Chang et al., respectively. EBER in situ hybridisation technique was applied for the detection of EBV in the tumours.
RESULTS: In this series of 32 cases of UAT DLBCL, 34% (11/32) were GCB, and 66% (21/32) were non-GCB types; 59% (19/32) had combined patterns A and B, and 41% (13/32) had pattern C. Statistical analysis revealed no significant difference in the occurrence of these prognostic subgroups in the UAT when compared with series of de novo DLBCL from all sites. There was also no site difference in phenotype protein expressions, with the exception of MUM1. EBER in situ hybridisation stain demonstrated only one EBV infected case.
CONCLUSIONS: Prognostic subgroup distribution of UAT DLBCL is similar to de novo DLBCL from all sites, and EBV association is very infrequent.
METHODS: We conducted a cross-sectional study by using 29 archived formalin-fixed paraffin embedded tissue blocks of DLBCL. All the samples were evaluated for the subgrouping of COO DLBCL was determined by expression of CD10, BCL6 and MUM1 based on Hans classification. In addition, expressions of c-MYC, BCL2 and BCL6 were detected by IHC.
RESULTS: Among the 29 cases, MYC, BCL2 and BCL6 proteins were detected in 72.4%, 62.1% and 62.1% of patients, respectively. Concurrent expression (c-MYC positive/BCL2 positive and/or BCL6 positive) was present in 58.6% of patients. 34.5% were categorised as germinal centre like (GCB) subgroup and 65.5% were categorised as nongerminal centre like (non-GCB) subgroup. Among the clinicopathological features, the double/triple protein expression lymphoma was significantly associated with elevated LDH level (p=0.018), IPI score (p=0.003), Ann Arbor stage (p=0.011) and complete response rate (p=0.011).
CONCLUSION: Double/triple protein lymphoma was strongly associated more adverse clinical risk factors. Thus, analyses of MYC, BCL2 and BCL6 expression by IHC represents a rapid and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.
AIMS OF THE STUDY: To analyse pre-treatment clinical features of DLBCL patients that are predictive of R-CHOP therapy resistance and early disease relapse after R-CHOP therapy treatment.
METHODS USED TO CONDUCT THE STUDY: A total of 698 lymphoma patients were screened and 134 R-CHOP-treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R-CHOP resistance/early relapse group and R-CHOP sensitive/late relapse group.
RESULTS OF THE STUDY: 81 of 134 (60%) were R-CHOP sensitive/late relapse, while 53 (40%) were R-CHOP resistance/early relapse. The median follow-up period was 59 months ± standard error 3.6. Five-year overall survival rate of R-CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R-CHOP resistance/early relapse [odds ratio = 5.268 (1.888-14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll-lV), raised pre-treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2-4) and high R-IPI score (3-5) showed no significant association with R-CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05).
CONCLUSION AND CLINICAL IMPLICATIONS: DLBCL patients with more than one extranodal site are 5.268 times more likely to be R-CHOP therapy resistance or experience early disease relapse after R-CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance.
MATERIALS AND METHODS: 51 cases of DLBCL paraffin-embedded tissue samples were retrieved from a single private hospital in Kuala Lumpur, Malaysia. EBER-ISH was performed to identify the EBV expression; ten EBV(+)-DLBCL cases subjected to immunohistochemistry for LMP1, pJAK1, pSTAT3 and MYC; FISH assay for c-MYC gene rearrangement.
RESULTS: Among 10 cases of EBV(+)-DLBCL, 90% were non-GCB subtype (p=0.011), 88.9% expressed LMP1. 40% EBV(+)-DLBCL had pJAK1 expression.
CONCLUSION: 66.7% EBV(+)-DLBCL showed the positivity of pSTAT3, which implies the involvement of EBV in constitutive JAK/STAT pathway. 44.5% EBV(+)-DLBCL have co-expression of pSTAT3 and MYC, but all EBV(+)-DLBCL was absence with c-MYC gene rearrangement. The finding of clinical samples might shed lights to the lymphomagenesis of EBV associated with non-GCB subtypes, and the potential therapy for pSTAT3-mediated pathway.
METHODS: ALK gene rearrangement was detected by immunostaining of ALK protein and fluorescence in situ hybridisation (FISH) targeting at the 2p23 region.
RESULTS: The expression of ALK protein was detected in 24/34 (71%) of the cases, and it was significantly higher in childhood cases (100%) when compared to adult cases (47%). The analyses by FISH were consistent with the results from immunostaining of ALK protein, but the analyses were only successful in 15/34 (44%) cases. FISH analyses detected extra copies of ALK gene in three cases, including one case that expressed ALK protein and showed 2p23 rearrangement.
CONCLUSIONS: The current series revealed a high frequency of ALK gene rearrangement, especially in the children. Immunostaining of ALK protein is a reliable indication of ALK gene rearrangement, and is superior to FISH. However, FISH analysis is useful in detecting other genetic aberrations that are not related to ALK gene rearrangement.