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Characteristics of CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors.

ABSTRACT: Aberrant expression of CD5 has been reported in 5-10% of diffuse large B-cell lymphomas (DLBCLs). CD5+ DLBCL had been recognized as an aggressive immunophenotypic subgroup of DLBCL in the 2008 WHO classification of haematolymphoid neoplasm; however, it was eliminated from the list of subgroups of DLBCLs in the revised 2016 classification. Nevertheless, there is much controversy regarding the clinical significance of CD5 expression, and many researchers still assert that this subgroup exhibits an extremely unfavorable prognosis with frequent treatment failure. We retrospectively investigated 405 DLBCLs recruited from three university hospitals in Korea from 1997 to 2013. The clinical profile, immunophenotype, and chromosomal structural alterations of the BCL2 and MYC genes were compared according to CD5 expression. A total of 29 cases of de novo CD5+ DLBCL were identified out of 405 in our series (7.4%). Clinicopathologic correlation was performed in all 29 CD5+ DLBCLs and 166 CD5- DLBCLs which were eligible for full clinical review and further pathologic examination. Compared with CD5- counterparts, CD5+ DLBCLs showed female preponderance, frequent bone marrow involvement, higher lactate dehydrogenase level, advanced Ann Arbor stages and poorer prognosis (all p<0.05). Pathologically, the expression of CD5 positively correlated with that of BCL2, MYC and Ki-67 (all p<0.05). Coexpression of BCL2 and MYC, which is referred to as a double-expressor, was relatively more common in CD5+ DLBCL, whereas translocation or amplification of these genes was very rare. in conclusion, the expression of CD5 is an independent poor prognostic factor of DLBCLs, and this subgroup displays unique clinicopathologic features. Although the exact mechanism remains uncertain, consistent activation of BCL2 and MYC by alternative pathways other than chromosomal translocation may contribute to the pathogenesis.

SUBMITTER: Na HY

PROVIDER: S-EPMC6808439 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Characteristics of CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors.

Na Hee Young HY Choe Ji-Young JY Shin Sun Ah SA Kim Hyun-Jung HJ Han Jae Ho JH Kim Hee Kyung HK Oh So Hee SH Kim Ji Eun JE

PloS one 20191023 10

Aberrant expression of CD5 has been reported in 5-10% of diffuse large B-cell lymphomas (DLBCLs). CD5+ DLBCL had been recognized as an aggressive immunophenotypic subgroup of DLBCL in the 2008 WHO classification of haematolymphoid neoplasm; however, it was eliminated from the list of subgroups of DLBCLs in the revised 2016 classification. Nevertheless, there is much controversy regarding the clinical significance of CD5 expression, and many researchers still assert that this subgroup exhibits an ...[more]

PMID: 31644584

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Project description:BACKGROUND:The poor outcome of high-grade B-cell lymphoma, with rearrangements of MYC, BCL2 and/or BCL6, also known as double-hit lymphoma or triple-hit lymphoma (DHL or THL), has been well documented, while the clinical significance of extra copies of MYC, BCL2 or BCL6 are still less well known. METHODS:In total, 130 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) were included in our study. Fluorescence in situ hybridization and immunohistochemistry were performed in all cases to evaluate the genetic status and protein expression levels of MYC, BCL2 and BCL6. RESULTS:Among the 130 cases of DLBCL, the prevalence rates of extra copies of MYC, BCL2 and BCL6 were 10.8, 20.0 and 14.6%, respectively, and the corresponding rates of gene rearrangement were 10.0, 14.6 and 16.9%, respectively. In total, 7.7% (10/130) of patients were DHL/THL; 9.2% (12/130) of patients were DLBCL with MYC and BCL2 and/or BCL6 gene abnormalities including rearrangements or extra copies, while excluded DHL/THL. The positive protein expression rates of MYC, BCL2 and BCL6 were 46.9% (61), 75.4% (98) and 70.0% (91), respectively. Among the 51 cases with MYC/BCL2 co-expression, 14 cases showed concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities, and the remaining 37 cases were classified as double-expressor lymphoma (DEL). MYC and BCL2 rearrangement and BCL2 extra copies were all associated with upregulated protein expression. Cases with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities were both associated with MYC/BCL2 co-expression. Patients with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities excluded DHL/THL had shorter OS (P?<?0.001) than patients with DLBCL with no genetic change, and showed no statistical different with patients with DHL/THL (P?=?0.419). Extra copies of MYC was independent prognostic factors for DLBCL. CONCLUSIONS:Patients with MYC and BCL2 and/or BCL6 gene extra copies might show a trend towards poor prognosis, and the detection of extra copies of MYC, BCL2 and BCL6 might deserve more attention.

Dataset Information

Characteristics of CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors.

Publications

Characteristics of CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors.

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