Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We identified the human germinal center-associated lymphoma (HGAL) in gene-expression profiling studies of diffuse large B-cell lymphoma (DLBCL). The expression of HGAL correlated with survival in patients with DLBCL. The HGAL gene is the human homolog of M17, a mouse gene expressed specifically in normal germinal center (GC) B cells. We generated a monoclonal antibody against the HGAL protein and show that HGAL is expressed in the cytoplasm of GC lymphocytes and in lymphomas of GC derivation. Among 727 lymphomas tested by immunohistochemistry on tissue microarrays, HGAL staining was found in follicular lymphomas (103 of 107), Burkitt lymphomas (40 of 40), mediastinal large B lymphomas (7 of 8), and in DLBCLs (103 of 151). Most marginal zone lymphomas lacked HGAL staining. Lymphocyte-predominant Hodgkin lymphomas (12 of 17) and, surprisingly, classical Hodgkin lymphomas (78 of 107) were found to be positive. Hierarchical clustering of comparative immunohistologic results in DLBCLs demonstrates that the expression of HGAL is similar to 2 other GC-associated proteins, BCL6 and CD10, but different from 2 markers associated with a non-GC phenotype, MUM1/IRF4 and BCL2. The restricted expression and GC specificity of HGAL protein suggest that it may have an important role in the diagnosis of specific lymphomas, and, potentially in the identification of subtypes associated with different prognoses.
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PMID:Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation. 1567 69

Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important categories such as germinal center B (GCB)-like and non-GCB-like groups. The t(14;18)(q32;q21) translocation defines a unique subset of DLBCL cases with a GCB gene expression profile. Two-color fluorescence in situ hybridization (FISH) analysis was applied to detect t(14;18) (q32;q21) in the nuclei of paraffin-embedded tissue sections from 61 patients with de novo DLBCL. Nine (15%) of 61 cases had a positive pattern. Fifty-seven cases were subclassified in an immunohistochemical study with anti-CD10, anti-bcl-6, and anti-MUM1 antibodies. In this classification, 21 cases (37%) were placed in the GCB group, and 36 (63%) were placed in the non-GCB group. There was a discrepancy between t(14;18) occurrence and bcl-2 protein expression. Bcl-2 protein expression was positive in 40 (67%) of 60 cases. The expression of bcl-2 protein in the GCB and non-GCB groups was not significantly different: 15 (71%) of 21 cases in the GCB group and 24 (67%) of 36 cases in the non-GCB group tested positive. We found no difference between the FISH-positive and FISH-negative groups in overall survival time (P = .6019, log-rank test). The overall survival rates of GCB and non-GCB groups did not differ significantly by immunohistochemical classification (P = .5399, log-rank test). Overall survival was significantly longer in the group with a low International Prognostic Index (IPI) score than in the group with a high IPI score (P = .0002, log-rank test). Our results suggest that immunohistochemical study and cytogenetic study with t(14;18) FISH cannot predict the clinical outcomes of DLBCL patients. A study with a larger number of patients may show a difference in clinical outcomes between FISH-positive and FISH-negative groups and between GCB and non-GCB groups.
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PMID:Incidence of diffuse large B-cell lymphoma of germinal center B-cell origin in whole diffuse large B-cell lymphoma: tissue fluorescence in situ hybridization using t(14;18) compared with immunohistochemistry. 1571 89

We immunohistochemically defined the histogenesis of posttransplantation lymphoproliferative disorders (PTLDs; B-cell phenotype) occurring after allogeneic T cell-depleted hematopoietic stem cell transplantation (HSCT; n = 15) or solid organ transplantation (SOT; n = 11) to determine whether transplantation type or morphologic subtype of PTLD affected the histogenetic subtype. Immunohistochemical stains using histogenetic markers for germinal center (GC) B cells, late GC and post-GC B cells, and post-GC B cells were performed on paraffin-embedded samples. Morphologically, 14 cases were polymorphic; 12 were monomorphic. Histogenetic marker expression was as follows: 1 monomorphic case (4%), GC phenotype expressing bcl-6 and CD10; 17 cases (65%; polymorphic, 9; monomorphic, 8), late GC-early post-GC phenotype expressing MUM1/IRF4; 8 cases (31%; polymorphic, 5; monomorphic, 3), post-GC phenotype expressing MUM1/IRF4 and CD138 but not bcl-6. PTLD cases after HSCT more frequently were post-GC phenotype than after SOT (7/15 vs 1/11, respectively; P = .040) and were independent of morphologic subclassification. Results suggest that most PTLDs are late GC-early post-GC phenotype with a minor group of post-GC phenotype and rare cases of GC phenotype. Findings also suggest a correlation between histogenetic phenotype of B-cell PTLD and type of transplantation.
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PMID:Histogenetic phenotypes of B cells in posttransplant lymphoproliferative disorders by immunohistochemical analysis correlate with transplant type: solid organ vs hematopoietic stem cell transplantation. 1576 85

Diffuse large B-cell lymphomas (DLBCL) represent the most common type of adult non-Hodgkin's lymphomas in Western countries and are characterized by heterogeneous clinical, histological, immunophenotypic and genetic features. Recent investigations using cDNA and oligonucleotide microarrays have identified molecularly distinct groups of DLBCL with respect to the B-cell differentiation gene expression profile: the germinal center (GC) B-cell-like DLBCL, the activated B-cell-like DLBCL and the type 3 DLBCL. The GC B-cell-like DLBCL were characterized by the expression of genes of the normal GC B-cells, the activated B-cell-like DLBCL were characterized by the expression of genes that are normally induced luring in vitro activation of peripheral blood B-cells, while the type 3 DLBCL did not express either set of genes at a high level. Patients with GC B-cell-like DLBCL had more favorable clinical outcome than those with activated B-cell-like or type 3 DLBCL. Immunohistochemical studies have shown that the bc16/CD10/MUM1/CD138 B-cell differentiation immunophenotypes are prognostically relevant and may predict the cDNA classification in a sizable fraction of DLBCL. In the last few years, there has been accumulating molecular and immunohistochemical evidence indicating links between B-cell differentiation gene expression profiles and expression of apoptosis and cell cycle-associated genes in DLBCL. The present review summarizes data with respect to the relationships between B-cell differentiation, apoptosis and proliferation in DLBCL.
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PMID:B-cell differentiation, apoptosis and proliferation in diffuse large B-cell lymphomas. 1581 58

This study was undertaken to analyze the differentiation profiles assessed by immunophenotyping in AIDS-related B-cell lymphoma (ARL) and their relation to the clinical course. Paraffin-embedded sections of 89 ARL cases during 1989 to 2004 were stained immunohistochemically with antibodies to CD3, CD10, CD20, CD38, CD138/Syndecan-1 (Syn-1), multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4), B-cell lymphoma protein-2 (BCL-2), BCL-6, latent membrane protein-1 (LMP-1), and Ki-67. Expression of CD10 and CD20 were associated with better overall survival (OS; P = .009 and P = .04, respectively). Expression of CD20 was associated with longer disease-free survival (DFS; P = .03), whereas expression of CD138/Syn-1 was associated with shorter DFS (P = .03). OS and DFS were worse in patients with immunophenotypic profiles related to post-germinal center (GC) differentiation (BCL-6 and CD10 negative, MUM1/IRF4 and/or CD138/Syn-1 positive) when compared with GC differentiation (P = .01). When controlled for age-adjusted International Prognostic Index (IPI), prior AIDS-defining illness (ADI), and year of ARL diagnosis, a post-GC differentiation remained significantly associated with poor OS and DFS. Expression of CD10 was associated with a preserved immunocompetence, whereas CD20 was less frequent in patients developing ARL while on highly active antiretroviral therapy (P = .04). In summary, lack of CD20 or CD10 expression and a post-germinal center signature are associated with a worse prognosis in ARL.
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PMID:AIDS-related B-cell lymphoma (ARL): correlation of prognosis with differentiation profiles assessed by immunophenotyping. 1590 93

Diffuse large B-cell lymphoma (DLBCL) has been shown to be comprised of at least two prognostic entities, depending on its resemblance to normal germinal center or activated B cells, using global gene expression profiling. Also, the expression patterns of bcl-6, CD10 and IRF-4 (also known as MUM1) have been suggested as alternative means of identifying the germinal- and nongerminal center (activated B-cell like) groups. In the present study, we evaluated by immunohistochemistry the expression patterns of CD10, bcl-6, IRF-4 and bcl-2 in a large material of 161 DLBCL patients. Using two different approaches, patients with germinal center phenotype displayed a significantly better survival than the nongerminal center group. Positive staining for bcl-6 or CD10 predicted for superior survival, while expression of IRF-4 alone showed no association with prognosis. Furthermore, expression of bcl-2 was associated with worse event-free survival and overall survival. In a multivariate analysis, a high international prognostic index score (3-5), non-GC phenotype and bcl-2 were independent adverse prognostic factors. Here we confirm the prognostic importance of determining the germinal- or nongerminal center phenotype in patients with DLBCL.
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PMID:Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis. 1592 May 53

Although diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, it is both clinically and morphologically heterogenous. The present study investigates the significance of survivin and a novel monoclonal antibody (MAb), T332, immunohistochemically for predicting the prognoses of DLBCL and its subtypes classified as germinal center B-cell-like type (GCB) and non-GCB type (NGCB) based on the expression profiles of CD10, bcl-6, and MUM1. A total of 60 cases of DLBCL (GCB, n = 22; NGCB, n = 38) were examined for the expression of survivin and T332 antigen. Survivin(+) DLBCL had a significantly worse prognosis (P = 0.01) than survivin(-) cases, as already reported, while survivin(+) GCB or NGCB tended to have poor prognoses (P = 0.06 and 0.07, respectively). However, T332(+) DLBCL and NGCB had significantly more unfavorable prognoses than T332(-) cases (P = 0.01 and 0.02, respectively) while there was no significant survival difference between the T332(+) and T332(-) groups of GCB (P = 0.11). Interestingly DLBCL coexpressing survivin and T332 (n = 13) had a significantly worse prognosis (P = 0.009) than the remaining single positive and double negative cases (n = 31). In conclusion, survivin and the novel MAb, T332, might be a good predictor of DLBCL and its subtypes.
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PMID:Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes. 1594 89

Most primary central nervous system lymphomas (PCNSLs) in immunocompetent patients are diffuse large B-cell lymphomas (DLBCLs), characterized by poor prognosis, compared with systemic forms. A germinal center B-cell-like (GCB) origin of PCNSL was hypothesized on the basis of BCL-6 expression and ongoing mutational activity. Our goal herein was to determine, for 83 PCNSLs, the percentages of GCB and activated B-cell-like (ABC) phenotypes and their prognostic significance. CD10, BCL-6, MUM1, BCL-2, and CD138 antigens were immunohistochemically labeled on paraffin-embedded sections; the first 4 were positive in 2.4%, 55.5%, 92.6%, and 55.5% of the tumors, respectively. None of the 56 tested samples expressed CD138. Among the 82 patients with complete information, 79 (96.3%) were classified as ABC; 42 (51.2%) expressed BCL-6+ MUM1+, suggesting an "activated GCB" origin; 33 (40.2%) were exclusively MUM1+, and the remaining 4 (4.9%) were negative for all markers tested. These findings provide new insights into interpreting the poor PCNSL prognostic, which may, in part, be due to biologic aggressiveness associated with its activated B-cell-like pattern. We postulate assigning PCNSL a histogenetic "time-slot," overlapping late GC and early post-GC, that could explain the predominant ABC phenotype observed.
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PMID:A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases. 1615 Sep 48

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.
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PMID:Germinal center and activated b-cell profiles separate Burkitt lymphoma and diffuse large B-cell lymphoma in AIDS and non-AIDS cases. 1620 84

The bcl6/CD10/MUM1/CD138 B-cell differentiation immunophenotypes were analysed in 101 cases of classical Hodgkin lymphomas (cHL) aiming to elucidate their histogenesis. Three major bcl6/CD10/MUM1/CD138 immunophenotypes were distinguished on the basis of the immunohistochemical positivity of Hodgkin and Reed-Sternberg (H/RS) cells: (a) the late germinal center (GC)/early post-GC B-cell-like immunophenotype (bcl6-/CD10-/MUM1+/CD138-); 59/101 cases (59%), (b) the post-GC B-cell-like immunophenotype (bcl6-/CD10-/MUM1+/CD138+); 24/101 cases (24%) and (c) the indeterminate immunophenotype (bcl6+/CD10-/MUM1+/CD138-: 14 cases and bcl6+/CD10-/MUM1+/CD138+: four cases); 18/101 cases (18%). The above findings indicate that H/RS cells in most cHL display bcl6/CD10/MUM1/CD138 immunophenotypes consistent with late GC/early post-GC or post-GC B-cell differentiation. In addition, H/RS cells in a small fraction of cHL display indeterminate bcl6/CD10/MUM1/CD138 immunophenotypic profiles which are characterized by simultaneous expression of GC, late GC/early post-GC and post-GC B-cell differentiation proteins. These immunophenotypic profiles do not correspond to the differentiation immunophenotypes of normal B-cells and their identification in a part of cHL suggests that the differentiation process of H/RS cells is not complete in a fraction of these cells and/or is still ongoing at the time of observation.
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PMID:B-cell differentiation immunophenotypes in classical Hodgkin lymphomas. 1639 74


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