Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most common non-Hodgkin lymphomas in Uganda are neoplasms of B-cell derivation. The field of B-cell lymphoma immunophenotype has rapidly progressed because of the increasing availability of markers applicable to routine sections. Although the latter have allowed the identification of distinctive lymphoma entities in the developed countries, such approach has not yet been used in Uganda. One hundred twenty-nine formalin-fixed, paraffin-embedded tissue samples from the Department of Pathology of Makerere University were used for tissue micro-array (TMA) construction. Four-micrometer-thick sections were cut from TMAs and stained with hematoxylin and eosin and Giemsa. They were also used for immunohistochemistry and in situ hybridization. According to morphology and immunohistochemistry, lymphoid neoplasms were classified as Burkitt's lymphoma (BL) (95 cases), diffuse large B-cell lymphoma (19 cases), mantle cell lymphoma (4 cases), and B-cell lymphoblastic lymphoma (1 case). In BL, a homogeneous phenotype (CD10(+), Bcl-6(+), Bcl-2(-), MUM1/IRF4-, and Ki-67 approximately 100%) and a stable Epstein-Barr virus integration were found. A distinctive and unusual feature was the frequent plasma cellular differentiation, along with the positivity for CD30 and CD138 (recorded in 35 and 43 cases, respectively). According to our findings, most non-Hodgkin B-cell tumors in Uganda are endemic BLs followed by diffuse large B-cell lymphomas. The rest consist of rare but clinically important entities such as mantle cell lymphoma and B-cell lymphoblastic lymphoma. The availability of TMAs and immunohistochemistry has enabled us to precisely categorize tumors that have so far been diagnosed in Uganda as "high-grade/aggressive" lymphomas on the basis of cell morphology alone.
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PMID:B-cell non-Hodgkin lymphomas in Uganda: an immunohistochemical appraisal on tissue microarray. 1843 78

Diffuse large B-cell lymphoma (DLBCL) can be subdivided into prognostically significant groups with germinal center B-cell-like (GCB), activated B-cell-like (ABC), and type 3 groups. In this study, tissue microarray slides composed of 163 de novo DLBCLs from Chinese patients were immunostained for CD20, CD10, Bcl-6, MUM1, CD138, Bcl-2, Ki-67, cyclin D3, geminin, and P27(Kip1). One hundred forty-nine of 163 DLBCLs could then be classified into GCB group (pattern A), activated GCB group (pattern B) and activated non-GCB group (pattern C) according to the expression of CD10, Bcl-6, MUM1, and CD138. Of the 149 cases, 40 (26%) showed pattern A expression and were grouped as GCB group, lower than reported frequency of the studies involving mostly Western population. Compared with cases with pattern A, those with pattern B (activated GCB group) and C (activated non-GCB group) more often presented with more aggressive tumors and a shorter survival time. These results indicate that most of DLBCLs from Chinese patients can be classified into prognostically different groups based on the antigenic expression models using a panel of GCB- and ABC-associated markers. Polymerase chain reaction analysis of t(14;18) showed that 11 of 64 cases were t(14;18)-positive, and most (10 of 11) of it occurred in the group with pattern A. The translocation was significantly associated with expression of Bcl-2 protein. The group with pattern B demonstrated more frequent expression of Ki-67, cyclin D3, geminin, and showed higher proliferative activity than the group with pattern A. These findings suggest that high proliferative activity of tumors with pattern B may be associated with aggressive tumor behavior and poor clinical outcome in patients with DLBCL.
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PMID:Clinicopathologic significance of immunophenotypic profiles related to germinal center and activation B-cell differentiation in diffuse large B-cell lymphoma from Chinese patients. 1844 May 93

Although approximately 10-20% cases of follicular lymphoma lack BCL2 gene rearrangement, there are few reports having described the alternative genetic aberrations and their association about clinicopathological features. In this study, analysis by Fluorescence in situ hybridization of BCL6 gene aberrations in 100 follicular lymphoma cases without IGH/BCL2 rearrangement resulted in the identification of four subgroups. Group I: BCL6 gene rearrangement (n=41); Group II: BCL6 gene amplification/3q27 gain (n=30); Group III: the absence of both (n=23); and Group IV: the presence of both (n=6). Group II showed higher grade morphology (Grade 3a/b: 93%), higher bcl2 and MUM1 expression (73 and 57%, respectively), and more frequent combination with BCL2 gene amplification/18q21 gain (90%) than the other groups. BCL6 gene aberration, especially amplification/3q27 gain, indicates the presence of certain morphological and phenotypical findings in follicular lymphoma cases without IGH/BCL2 rearrangement.
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PMID:BCL6 gene amplification/3q27 gain is associated with unique clinicopathological characteristics among follicular lymphoma without BCL2 gene translocation. 1850 Feb 67

Follicular lymphoma (FL) is one of the most common subtypes of non-Hodgkin lymphoma and frequently transforms to diffuse large B-cell lymphoma (DLBCL). To clarify some aspects of the natural history of FL, we retrospectively examined 43 consecutive patients who had DLBCL with pre- or coexisting FL grade 1 or 2. The patients comprised 22 men and 21 women with a median age of 53 years. Most of the patients (34/43) showed advanced-stage (III or IV) disease initially. We examined both FL and DLBCL components morphologically, immunohistochemically, and by interface fluorescence in situ hybridization (FISH: IGH/BCL2 fusion, BCL6 translocation) analysis. Most of the DLBCLs were classified as the centroblastic subtype, with two exceptions of the anaplastic subtype. Immunohistochemical analysis of both the FL and DLBCL components revealed the following respective positivity rates: CD20 100%/100%, CD10 86%/66%, Bcl-2 96%/91%, Bcl-6 84%/88%, MUM1 16%/34%, CD30 0%/20%, CD138 0%/0%, and CD5 0%/3%. Loss of CD10 (6/36, 17%) and gain of MUM1 (7/28, 25%) and CD30 (5/21, 24%) through transformation were not infrequent. High positivity rates for Bcl-2 and Bcl-6 were maintained throughout transformation. Among the DLBCLs, 84% were classified as the germinal center B-cell phenotype (GCB) and 16% as non-GCB in accordance with the criteria of Hans et al. IGH/BCL2 fusion was detected by FISH in 89% of FLs and 82% of DLBCLs. BCL6 translocation was detected in 1/6 (17%) DLBCLs without IGH/BCL2 fusion. Thus, although the morphological features and FISH results for DLBCL were consistent with transformed FL, the immunophenotype showed wide heterogeneity.
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PMID:Diffuse large B-cell lymphoma after transformation from low-grade follicular lymphoma: morphological, immunohistochemical, and FISH analyses. 1854 5

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The immunohistochemistry-based algorithms for the determination of the cell of origin of DLBCL have been proposed as a practical method to validate and surrogate results obtained by gene expression profiling. We studied 71 patients with primary nodal DLBCL at diagnosis, who received anthracycline-based therapy with or without rituximab. Immunohistochemistry was performed using anti-CD10, Bcl-6, MUM1 and Bcl-2 antibodies in order to assess the ontogenic profile of neoplastic cells and to verify its relation with clinical outcome. Survival data were analysed using an explorative Cox model. The immunohistochemistry-based algorithms for the determination of the cell of origin of DLBCL were not associated with prognosis. By contrast, Bcl-6 expression was associated with a longer lymphoma-free survival while immunoreactivities for MUM1 or Bcl-2 were not significantly related to patient outcome. Bcl-6 expression alone proved to be a prognostic marker in primary nodal DLBCL and seemed to be more reliable to predict clinical outcome in these disorders than the immunohistochemical algorithms for the detection of the germinal centre/non-germinal centre immunophenotype.
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PMID:Bcl-6 protein expression, and not the germinal centre immunophenotype, predicts favourable prognosis in a series of primary nodal diffuse large B-cell lymphomas: a single centre experience. 1860 21

Diffuse large B-cell lymphomas can be considered primary bone tumors if they are monostotic or polyostotic, affecting multiple skeletal sites without visceral or lymph node involvement. They are rarely considered as extranodal lymphomas or as bone tumors, respectively. To elucidate the prognostic relevance of clinicopathologic characteristics in such disease, we collected a cohort of primary diffuse large B-cell lymphomas of the bone and retrospectively investigated 33 patients. The cohort encompassed the years 1975 to 2004. Protein expression patterns were identified by immunohistochemistry applied to a tissue microarray. The patients included 23 males (mean age, 37 years) and 10 females (mean age, 54 years). Disease stage was I and II in 30 and IV in 3 patients. Within the mean follow-up of 28 months, 6 patients died. Median overall survival was reached after 78 months. Clinical factors favoring a good prognosis were age younger than 53 and administration of chemotherapy. Of the phenotypic markers analyzed (CD10, CD44s, CD138, Bcl-2, Bcl-6, MUM1, and Ki-67), MUM1 expression in more than 10% of the tumor cells and CD10 expression in less than 55% as well as a nongerminal center signature substantiated adverse outcome in a univariate model. In summary, poor survival in PB-DLBCL was clearly predicted in patients older than 53, who had not received chemotherapy, and who demonstrated MUM1 expression and nongerminal center phenotype.
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PMID:Primary diffuse large B-cell lymphomas of the bone: prognostic relevance of protein expression and clinical factors. 1861 98

Although diffuse large B cell lymphomas (DLBCL) are considered in the WHO classification a specific histopathological type, their diversity in the clinical features, morphology and molecular aberrations strongly suggest that these tumors represent a heterogeneous group of neoplasms rather than a single clinicopathological entity. There have been various approaches to differentiate between separate nosological entities within DLBCLs based on various methods, such as the microarray technique or immunohistochemistry. Although it has been proven that gene expression profiling using cDNA microarrays could identify prognostically important subgroup of DLBCL: germinal center B-cell (GCB)-like DLBCL and activated B-cell (ABC)-like DLBCL, this method is impractical as a clinical tool. Therefore, investigators have started using immunohistochemistry in their studies. Employing various immunohistochemical antibodies, such as CD10, CD138, anti-Bcl-2, anti-Bcl-6, MUM1 and anti-p53, several groups have aimed at subclassifying DLBCL into the GCB and ABC subgroups with comparable differences in clinical behavior. This review summarizes these data and indicates their impact on DLBCL classification.
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PMID:Usefulness of immunohistochemistry in identification of prognostically important subgroups (GCB and ABC) in a heterogeneous group of diffuse large B-cell lymphomas--a review article. 1909 55

Gene expression profiling studies initially enabled diffuse large B-cell lymphoma to be divided into germinal center and activated B-cell-like subtypes, which define high- and low-risk patient groups when treated with chemotherapy. Attempts to reproduce the prognostic classification immunohistochemically have, however, provided inconsistent results. The aim of this study was to determine whether modified immunohistochemical classification of cell of origin focusing on activated B-cell-like markers could be used to predict the outcome of immunochemotherapy-treated diffuse large B-cell lymphoma patients. The expression of CD10, Bcl-6, MUM1/IRF4, Bcl-2, and FOXP1 was determined immunohistochemically from 88 samples of diffuse large B-cell lymphoma patients treated uniformly with R-CHOP. When the modified classification using MUM1/IRF4 and FOXP1 positivities as activated B-cell-like markers was applied to distinguish the patients between the activated B-cell-like and other diffuse large B-cell lymphoma subtypes, a significantly worse outcome was seen for the patients with the activated B-cell-like phenotype (3-year failure-free survival 63 vs 82%, P=0.048, overall survival 69 vs 85%, P=0.110). Similarly, according to the Muris algorithm, the group 2 patients representing Bcl-2-positive post-germinal center patients showed an inferior outcome in comparison to the group 1 patients (failure-free survival 59 vs 81%, P=0.041, overall survival 67 vs 82%, P=0.159). In contrast, when the classification of the same cohort was performed according to the Hans algorithm, no significant difference in survival was observed between the germinal center and non-germinal center patients. In conclusion, the data suggest that both the modified activated B-cell-like and Muris classifications define the non-germinal center phenotype as an adverse risk factor in R-CHOP-treated diffuse large B-cell lymphoma patients.
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PMID:Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP. 1944 93

We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) +/- rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl-6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 (P = 0.001) or MUM1 (P = 0.011), or non-GCB subtype (P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R-CHOP group (P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated.
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PMID:Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. 1965 56

A number of biomarkers, particularly proteins that contribute to prognosis in diffuse large B cell lymphoma (DLBCL), have been identified. However, translation into accepted standards to predict survival has not yet been accomplished, primarily due to contradictory reports in the literature resulting from, among other factors, arbitrary methodologies used to set cut-off values for determining positivity. Some of these problems might be resolved by application of rational statistical methods for determination of cut-off scores. Herein, we critically address issues on in situ phenotypic prognostic tumor-related biomarkers in DLBCL with a particular and practical emphasis on tools for cut-off level determination, especially receiver operating characteristic curve analysis. Moreover, we candidly illustrate the application of these tools for efficient disease-specific survival prognostication on a tissue microarray collective of 240 primary DLBCL using the common prognostic biomarkers Bcl-2, Bcl-6, CD10, FOXP1, MUM1, and Cyclin E. Comparison of the results relative to disease-specific survival unequivocally showed the superior discriminatory power of the cut-off levels calculated by receiver operating curves and the Youden's index, compared to arbitrary cut-off values from the literature, advocating fundamental application of rational methods for determination of clinically relevant prognostic biomarkers' cut-off scores.
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PMID:Prognostic immunophenotypic biomarker studies in diffuse large B cell lymphoma with special emphasis on rational determination of cut-off scores. 1992 52


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