Prognostic values of myeloid differentiation factor 88 (MYD88) and transducin (β)-like receptor 1 (TBLR1) expression in tissues of diffuse large B-cell non-Hodgkin lymphoma patients – an immunohistochemical study (original) (raw)
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Blood, 2017
Overexpression of the BCL2 is associated with a poor prognosis in diffuse large B-cell lymphoma (DLBCL). The assessment of MYC immunohistochemistry (IHC) is becoming optimized, whereas the criteria for BCL2 positivity are highly variable. Furthermore, data on the frequency and prognostic value of BCL2 positivity are conflicting. We aimed to evaluate BCL2 expression by IHC and assess the prognostic significance of the histopathologically-scored BCL2 expression in 456 patients with DLBCL uniformly treated with standard immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP). We initially designed four-grade BCL2 scoring criteria, from 0 to 3+, and found that approximately 40% of DLBCL showed strong BCL2 expression (score 3+). The scores from the pathologist's visual estimation were confirmed to be reliable using a digital image analysis. A retrospective survival analysis revealed that BCL2 score 3+ was a significant prognostic factor ...
Cancers
Diffuse large B-cell lymphoma (DLBCL) patients with MYC/BCL2 double expression (DE) show poor prognosis and their clinical outcomes after R-CHOP therapy vary immensely. We investigated the prognostic value of DE in aggressive B-cell lymphoma patients (n = 461), including those with DLBCL (n = 417) and high-grade B-cell lymphoma (HGBL; n = 44), in a prospectively immunoprofiled cohort. DE was observed in 27.8% of DLBCLs and 43.2% of HGBLs (p = 0.058). DE-DLBCL patients were older (p = 0.040) and more frequently exhibited elevated serum LDH levels (p = 0.002), higher international prognostic index (IPI; p = 0.042), non-germinal-center B-cell phenotype (p < 0.001), and poor response to therapy (p = 0.042) compared to non-DE-DLBCL patients. In R-CHOP-treated DLBCL patients, DE status predicted poor PFS and OS independently of IPI (p < 0.001 for both). Additionally, in DE-DLBCL patients, older age (>60 years; p = 0.017), involvement of ≥2 extranodal sites (p = 0.021), bone marro...
Clinical cancer research : an official journal of the American Association for Cancer Research, 2016
Mutations in MYD88 are found in different lymphoproliferative disorders associated with particular biological characteristics and clinical impact. The aim of this study was to analyze the incidence of MYD88 mutations and its clinical impact in diffuse large B-cell lymphoma (DLBCL). The incidence, clinico-biological features and outcome of 213 patients (115M/98F; median age 65 years) with DLBCL treated with immunochemotherapy in a single institution according to MYD88 mutational status as assessed by an allele-specific PCR assay were analyzed. The cell of origin (COO) was determined in 129 cases by gene expression. MYD88 mutations were found in 47 cases (22%) including L265P in 39 and S219C and M232F in 4 cases, respectively. Patients with MYD88 L265P were older, presenting frequent extranodal involvement and mostly corresponded to activated B-cell like (ABC) subtype whereas no preference in COO was observed in patients with other MYD88 mutations. Five-year overall survival (OS) for ...
Blood Advances, 2019
In advanced-stage diffuse large B-cell lymphoma (DLBCL), the presence of an activated B-cell phenotype or a non–germinal center (GCB) phenotype, coexpression of MYC and BCL2 by immunohistochemistry, and the cooccurrence of MYC and BCL2 or BCL6 rearrangements are associated with inferior outcomes. It is unclear whether these variables remain prognostic in stage I/II patients. In this retrospective study, we evaluated the prognostic impact of cell of origin (COO), as well as dual-expressor (DE) status and molecular double-hit (DH) status, in stage I/II DLBCL by positron emission tomography with computed tomography (PET-CT). A total of 211 patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)–like regimens, with or without radiotherapy, was included. The median follow-up in the entire cohort was 4 years (range, 0.4-9.4), with estimated 4-year progression-free survival (PFS) and overall survival (OS) rates of 85% (95% confidence interval [C...
Blood, 2019
Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and a heterogeneous disease with a variety of molecular aberrations and diverse clinical outcomes. BCL2 expression has been implicated for a poor prognosis among patients with DLBCL. However, there is no consensus regarding the interpretation of BCL2 expression in DLBCL. In previous studies, the range of BCL2-positive cases, determined by immunohistochemistry (IHC), was highly variable (24 - 80%) due to subjective and semiquantitative interpretation and the absence of the established cutoff value for BCL2 expression. Consequently, the prognostic impact of BCL2 varies between studies. In addition, only the proportion of BCL2 positive tumor cells are considered in determining the BCL2 positivity. We aimed to define BCL2 positivity by quantitative analysis integrating both the intensity and proportion of BCL2 expression. Methods We retrospectively collected formalin-fixed, paraffin-emb...
Annals of Hematology, 2004
The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.
Cancer science, 2016
Genomic alterations and protein expression levels have been established as prognostic factors for survival in patients with diffuse large B-cell lymphoma (DLBCL). In particular, double-hit DLBCL (DHL), which exhibits translocations in MYC and BCL2 and/or BCL6, is known to be associated with a poor prognosis. However, the clinical significance of gene alterations and protein expression levels for MYC, BCL2, and BCL6 are unclear. In this study, we analyzed 61 adult patients diagnosed with DLBCL without DHL, who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) or R-CHOP-like regimens. There were no differences in the distribution of MYC expression rates among the different MYC gene statuses. In log-rank tests, MYC translocation was a prognostic factor for overall survival (OS; P = 0.011), whereas BCL2 and BCL6 translocation were not prognostic indicators (P = 0.999, P = 0.925, respectively). Although the expression levels of MYC and BCL...
Asian pacific journal of cancer prevention, 2019
Background: Due to lack of availability of gene expression profiling (GEP) for most developing countries and clinicians; the immunohistochemistry (IHC) is mostly used in the clinical application. The aim of our study is to check the possibility of using IHC to detect MYC and BCL2 in our patients with diffuse large B-cell lymphoma (DLBCL) instead of GEP to stratify them into high and low-risk groups. This will help in a proper treatment choice of subsequent improvement in the survival outcome. Method: During the study period, 90 DLBCL patients were eligible. MYC and BCL2 evaluated by IHC and gene rearrangement by real-time PCR (RT-PCR) and correlated with clinical-pathological features and survival. Results: Through IHC, the expression of MYC, BCL2, and double expression was detected in 35.6%, 46.7% and 30% of patients, respectively. While by RT-PCR, it was 4.53±0.74 for MYC compared with 2.18±0.78 for BCL-2. Most patients with BCL2+/MYC+; double-expressor and double-hit lymphomas (DEL and DHL) had high stage (III, IV), more extra-nodal involvement, (P value <0.001) and intermediate to high International Prognostic Index (IPI) risk profile (P-value <0.001). The median overall survival was 14 months and 6 months for DEL and DHL, respectively. While all patients with DHL died during the follow-up period, the median PFS were only 2 months for DEL. There was a statistically significant correlation between mRNA of MYC and BCL2 with their protein expression (p<0.001). Conclusion: Our results confirmed the unique characters and poor outcome associated with DEL and DHL mandated the need for more intense therapy and not the standard protocol. Moreover, the significant correlation between protein overexpression and gene rearrangement may open the door for the possibility to use IHC instead of RT-PCR in developing countries.