Dataset Information

MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.

ABSTRACT: Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH) score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336 de novo DLBCL, NOS treated with CHOP or R-CHOP. Breaks in MYC and BCL6, and fusion in IGH/BCL2 were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (?40%), BCL2 (?70%) and BCL6 (?50%) was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs) and triple-hit score (THS) were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI) score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts (P<0.05). The highly significant correlations with OS and PFS were maintained in multivariate models that controlled for IPI (P<0.05). DLBCLs with high DHSs and high THS share the clinical features and poor prognosis of double-hit lymphoma (P>0.05). These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP.

SUBMITTER: Yan LX

PROVIDER: S-EPMC4121314 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.

Yan Li-Xu LX Liu Yan-Hui YH Luo Dong-Lan DL Zhang Fen F Cheng Yu Y Luo Xin-Lan XL Xu Jie J Cheng Jie J Zhuang Heng-Guo HG

PloS one 20140804 8

Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH) score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangeme ...[more]

PMID: 25090026

Similar Datasets

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.

Project description:This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover, ~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.

Dataset Information

MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.

Publications

MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets