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)

Primary testicular lymphomas typically occur in patients over 60 years of age. Most are diffuse large B-cell lymphomas with frequent dissemination and a poor prognosis. Primary follicular lymphoma of the adult testis has not been well characterized. However, a small number of primary testicular follicular lymphomas have recently been described in children. These showed stage 1E disease, a lack of BCL2 gene rearrangement and Bcl-2 protein expression, and a good clinical outcome. Here, we describe 5 cases of primary follicular lymphoma of the testis and epididymis in adults. These presented as unilateral testicular masses 12 to 40 mm in diameter and were characterized histologically by small neoplastic follicles in a sclerotic background. The neoplastic cells expressed CD10 and Bcl-6, but not Bcl-2 and lacked t(14;18)(q32;q21)/IGH-BCL2 and BCL6 gene rearrangements. Four of the five patients were 35 years old or younger, and 4 presented with stage 1EA disease. Although follow-up is 12 months or less in 2 of the 5 patients, to date each has followed an indolent clinical course. These features are different from those of most adult nodal follicular lymphomas but are very similar to those of the pediatric primary testicular follicular lymphomas. Together, the pediatric and adult cases represent a discrete clinicopathologic entity of t(14;18)(q32;q21)/IGH-BCL2-negative primary follicular lymphoma of the testis and epididymis, which typically present as clinically indolent localized disease in young males and should be distinguished from the diffuse large B-cell lymphoma more frequently seen in the testes of older adults.
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PMID:Primary follicular lymphoma of the testis and epididymis in adults. 1759 72

Diffuse large B-cell lymphoma (DLBCL) is a frequent lymphoma subtype with a heterogeneous behavior and a variable response to conventional chemotherapy. This clinical diversity is believed to reflect differences in the molecular pathways leading to lymphomagenesis. In this study, we have analyzed pretreatment, diagnostic samples from 108 DLBCL by immunohistology for expression of four markers linked to germinal center B-cells (CD10, Bcl-6), postgerminal center B-cells (MUM1) and apoptosis (Bcl-2). The results indicate that both CD10 and Bcl-6 are favorable prognostic indicators, in contrast to Bcl-2, which is an adverse parameter. Furthermore, using two algorithms for distinction between low- and high-risk patients proposed by Hans et al. (Blood, 2004; 103:275) and Muris et al. (Journal of Pathology, 2006; 208:714), it is shown that both are useful for predicting outcome in DLBCL. However, in this report, the algorithm of Hans et al. was superior to that of Muris et al. These findings confirm and extend other studies and indicate that different prognostic subgroups of DLBCL can be distinguished by simple immunohistological investigations for a limited number of markers. Whether these groups are also relevant for individual treatment decisions will be important to investigate in prospective studies.
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PMID:Profiling of diffuse large B-cell lymphoma by immunohistochemistry: identification of prognostic subgroups. 1798 9

Primary central nervous system (PCNS) diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin's lymphoma whose growth is restricted to the central nervous system and eye. Primary CNS DLBCL has a poor prognosis relative to other extranodal DLBCL. Recently DLBCL has been subclassified as germinal and non-germinal center B-cell types using microarray. Germinal center B-cell DLBCL is associated with better prognosis compared to non-germinal center B-cell group. The objective of the study was to subcategorize the PCNS DLBCL into germinal center and non-germinal center DLBCL using immunohistochemistry and to correlate its prognostic significance. 21 immunocompetent patients were diagnosed with PCNS DLBCL over last 20 years at William Beaumont Hospital. Clinical data on outcome were collected and their specimens were retrieved. Immunohistochemical staining was done using markers, CD20, CD10, Bcl-6, MUM-1, MIB-1, Bcl-2 and by molecular analysis of the immunoglobulin heavy chain gene (IgH) variable region. Immunohistochemistry showed 1/21 (positive cases/examined cases) for CD10, 19/21 for Bcl-6, 19/21 for MUM-1 and 15/21 for Bcl-2. The expression pattern of CD10(-) MUM-1(+) is corresponded to the non-germinal center DLBCL. The MIB-1 index ranged from 40--80% with a mean of 57%, indicating a high proliferation of lymphoma cells. The IgH gene variable region analysis showed monoclonality in 15 of 21 cases (71%). Primary CNS DLBCL has a non-germinal center B-cell phenotype in majority of cases and has a high Bcl-2 positivity and MIB-1 index. These features might be associated with poor prognosis.
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PMID:Activated B-cell immunophenotype might be associated with poor prognosis of primary central nervous system lymphomas. 1825 70

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

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

We sought to determine the clinical and immunohistopathological prognostic factors for overall survival (OS) in adult patients with post-transplant lymphoproliferative disorders (PTLDs). Eighty-four patients diagnosed with PTLDs between 1980 and 2004 at the University of Pittsburgh Medical Center were identified. Immunohistochemical staining was performed on tumor tissue at the time of diagnosis for the following proteins: Bcl-2, Bcl-6, c-myc and p53. The median survival for all patients was 20.8 months, 95% CI: (7.4-77.6). On univariate analysis for OS, the following poor prognostic factors were identified: age at transplant >60 years (p = 0.024), multiorgan transplant (p = 0.019), ECOG > 2 (p < 0.0001), grafted organ involvement (p < 0.0001), extranodal disease (p = 0.011), early (<1 year) PTLDs (p < 0.0001), stage IV (p = 0.0017), EBV positive (p = 0.012) and elevated white blood count (p = 0.010). Good prognostic factors included ECOG<2 (p < 0.0001), late (>1 year) PTLDs (p = 0.002), early stage at diagnosis (stages I and II, p = 0.005), nodal disease (p = 0.0053), monomorphic disease (0.0034), initial immunosuppression reduction (p = 0.0015) and use of rituximab (p = 0.045). Bcl-2 but not Bcl-6, c-myc, or p53 correlated with poor survival, p = 0.0036. This study identifies new clinical and pathological markers for poor survival in PTLDs.
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PMID:Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders in solid transplant. 1879 8

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


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