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

Primary cutaneous B-cell lymphomas displaying a prominent follicular growth pattern are rare and remain poorly defined, particularly in terms of the frequency of detection of t(14;18) and whether or not, as a group, they represent an entity distinct from follicular lymphoma arising in lymph nodes. The morphologic, immunophenotypic, and clinical features of 16 cases of primary cutaneous follicular lymphoma, identified during a review of all PCBCL in the Scotland and Newcastle Lymphoma Group database, were studied and the number of cases harboring t(14;18) assessed by polymerase chain reaction using primers to the major breakpoint cluster region. Comparisons were made with stage I follicular lymphoma arising in lymph nodes and follicular lymphoma secondarily involving the skin. All cases of primary cutaneous follicular lymphoma had undergone thorough staging, including physical examination and CT scans of chest and abdomen, with 15 of 16 cases also having bone marrow aspiration and/or trephine performed. The morphology and immunophenotype of the lesions were similar to that expected in lymph nodes. All cases displayed a follicular architecture complete with follicular dendritic cell networks and comprised an admixture of CD10 and/or bcl-6-positive neoplastic centrocytes and centroblasts with 13 of 16 cases also expressing bcl-2 protein. None harbored t(14;18), a significantly different finding compared with cases of stage I nodal follicular lymphoma (p <0.001) and secondary cutaneous follicular lymphoma (p <0.039). Relapses occurred in five of 15 patients with a median time to first relapse of 20 months (range 1-73 months; mean 27.2 months). These were multiple in two patients and involved extracutaneous sites in two patients. The propensity for relapse was similar to that in a comparative cohort of stage I nodal follicular lymphoma, but the group of primary cutaneous follicular lymphoma were significantly more likely to attain complete remission; all cases of primary cutaneous follicular lymphoma were in complete remission when last seen compared with 49 of 87 patients with stage I nodal follicular lymphoma (p <0.005). No lymphoma-related deaths were encountered in 15 cases with a mean follow-up >60 months (range 5-119 months). These results support the concept of a subtype of follicular lymphoma lacking t(14;18) involving the major breakpoint cluster region, and with a propensity to arise in the skin. Despite a high relapse rate patients with primary cutaneous follicular lymphoma are more likely to achieve complete remission and may ultimately have a more favorable long-term prognosis than those with equivalent nodal disease.
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PMID:Primary cutaneous follicular lymphoma: a clinicopathologic and molecular study of 16 cases in support of a distinct entity. 1202 77

It is generally accepted that Epstein-Barr virus (EBV) latent genes EBNA-2, EBNA-3A, -3C, EBNA-LP and LMP1 are essential for growth transformation and immortalization of B lymphocytes. Among these genes, LMP1 plays a key role in the survival and dissemination of the infected B cells by inducing anti-apoptotic genes and surface expression of several activation antigens and adhesion molecules. We have previously shown that antisense oligodeoxynucleotides directed to LMP1 mRNA, effectively suppress LMP1 gene expression and substantially reduce B95.8 cell proliferation. In this study, we have used antisense LMP1 oligomers to investigate whether LMP1 suppression might influence the expression of latent EBV genes with oncogenic potential, anti-apoptotic genes, or affect the phenotype of EBV-infected B95.8 cells. Our data show that LMP1 suppression does not affect the transcription of EBNA-2, EBNA-3A, -3B and -3C genes, or that of bcl-2 and mcl-1 anti-apoptotic genes. In contrast, consistent modifications in the expression of CD39, CD54, CD23, CD11 and CD10 molecules were observed in B95.8 cells after treatment with antisense LMP1. Our findings support the possibility for using LMP1 antisense oligomers as therapeutics in EBV-associated tumors.
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PMID:Antisense to Epstein Barr Virus-encoded LMP1 does not affect the transcription of viral and cellular proliferation-related genes, but induces phenotypic effects on EBV-transformed B lymphocytes. 1203 73

Follicular lymphoma (FL) is a low-grade lymphoma that typically lacks CD5 antigen expression. We report 3 cases of FL with unusual expression of CD5. All cases showed histologic features of FL, including effaced nodal architecture, follicular growth pattern, and a spectrum of grades from 1 to 3 using World Health Organization criteria. In flow cytometric studies, all 3 cases showed a light chain-restricted, CD19+, CD20+ B-cell population coexpressing CD10 and low-level CD5. Immunohistochemical studies demonstrated an identical B-cell immunophenotype with weak expression of CD5 and coexpression of bcl-2 protein and the germinal center-associated markers, CD10 and bcl-6 protein. None of the cases showed expression of CD43, cyclin D1, or IgD. By molecular analysis, immunoglobulin heavy chain gene rearrangements were demonstrated in all 3 cases, and 2 of 3 cases had a t(14;18). These cases highlight the difficulty classifying these lymphomas by flow cytometric studies alone and emphasize the importance of recognizing FL in the differential diagnosis of CD5+ B-cell lymphomas.
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PMID:CD5+ follicular lymphoma: a clinicopathologic study of three cases. 1237 47

This study analyzes the pathologic and molecular features of 5 cases of primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg), recently included in the European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphoma. PCLBCL-leg accounts for 5% to 10% of all primary cutaneous B-cell lymphoma (PCBCL), usually affects elderly patients and carries a worse prognosis than other forms of PCBCL. It has been proposed that the malignant cells of PCLBCL-leg originate from germinal center (GC)-related cells, but their effective normal counterpart is unclear, and the rationale behind the inclusion of this lymphoma as a separate entity is based on its prognosis rather than on its proved histogenesis. All of our cases of PCLBCL-leg morphologically resembled diffuse large B-cell lymphoma (DLBCL), but to better define their histogenesis, we also analyzed various phenotypic and genotypic markers, including mutations of the Ig and of BCL-6 genes, as well as expression of the bcl-6, MUM1, and CD138/syndecan-1 proteins. Immunohistochemically, all of our cases stained for the L-26/CD20cy and CD79a antigens and expressed the bcl-2, bcl-6, and MUM-1 proteins but were negative for both the CD10/CALLA and CD138 antigens. With respect to molecular analysis, the lymphoma population of all PCLBCL-leg carried hypermutation of Ig genes, and all but 1 case also harbored mutations of the BCL-6 gene. Our results indicate that PCLBCL-leg are similar both under the morphofunctional and molecular profiles to most DLBCL of other sites. Thus, caution seems justified before definitely considering PCLBCL of the leg as a distinct entity.
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PMID:Primary cutaneous large B-cell lymphoma of the leg: histogenetic analysis of a controversial clinicopathologic entity. 1237 21

To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), we studied 128 patients (59 men, 69 women; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution. Cells from each patient were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67 antibodies. Four immunophenotyping profiles were distinguished according to the pattern of differentiation: germinal center-CD10(+) (GC-CD10(+); CD10(+)/Bcl-6(+)/MUM1(-)/CD138(-)), germinal center-CD10(-) (GC-CD10(-); CD10(-)/Bcl-6(+)/ MUM1(-)/CD138(-)), post-germinal center (pGC; CD10(-)/bcl-6(+/-)/ MUM1(+)/CD138(-)), and plasmablastic (CD10(-)/bcl-6(-)/MUM1(+)/CD138(+)). Rearrangement of bcl-2 was studied by polymerase chain reaction (PCR) in 57 patients. Single-antigen expression was as follows: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. Distribution according to differentiation profiles was as follows: GC-CD10(+), 24 patients, GC-CD10-, 30 patients; pGC, 60 patients; plasmablastic, 2 patients; other patterns, 12 patients. The pGC profile was associated with primary nodal presentation and immunoblastic morphology, whereas GC-CD10(+) tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 proliferative index. GC-CD10(-) patients more often presented with primary extranodal origin, early stage, normal lactic acid dehydrogenase (LDH) levels, and low or low/intermediate International Prognostic Index (IPI) scores than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Expression of bcl-2 was associated with advanced stage, high or high-intermediate IPI, and poor OS. Expression of bcl-2 maintained predictive value in multivariate analysis, with stage and LDH. In conclusion, differentiation profile was associated with particular clinicopathological features but was not essential to predicting outcome in DLBCL patients.
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PMID:Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. 1239 66

CD10, a proteolytic enzyme seen in germinal center cells and in the majority of follicular lymphomas, is occasionally expressed in diffuse large B-cell lymphomas (DLBCL). To clarify the origin and cellular characteristics of CD10-positive DLBCL, we analyzed 36 de novo cases of DLBCL for somatic mutations of the immunoglobulin heavy chain variable region (VH) genes and for their immunophenotypes. Expression greater than that of grade 2 Bcl-6 was observed in 11 of the 30 CD10-negative cases (37%) and in all six CD10-positive cases (100%; P < 0.05) without expression of CD5, CD23, cyclin D1, CD30 or CD138. The average mutation frequencies of the six CD10-positive and 30 CD10-negative DLBCL were 12.9 and 9.8%, respectively. The range of SM frequencies in CD10-positive DLBCL (9.52-18.06) was distinctly narrower than that observed for CD10-negative DLBCL (0.69-26.89). These findings seem to indicate that CD10-positive DLBCL, originating from germinal center B cells, is a genetically and immunophenotypically more homogeneous group than CD10-negative DLBCL. Furthermore, three extranodal lymphomas, in five of the six CD10-positive DLBCL, showed ongoing mutation, indicating that antigen-driven, high-affinity somatic mutation may play an important role in clonal expansion in CD10-positive DLBCL. All four extranodal cases of the six CD10-positive DLBCL showed ongoing mutation and/or bcl-2/JH rearrangement. This result suggests that the cell origin of extranodal CD10-positive DLBCL may be the same as that of follicular lymphomas.
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PMID:Analysis of immunoglobulin VH genes in CD10-positive diffuse large B-cell lymphoma. 1240 88

The incidence of B-cell non-Hodgkin lymphomas (B-NHL) at nodal and extranodal sites is fairly different. Follicular lymphomas (FL) occur predominantly at nodal sites and rarely in the gastrointestinal tract, while marginal zone lymphomas (MZL) of the mucosa-associated lymphatic tissue (MALT) type predominate in the digestive organs and especially in the stomach. We report a 72-year-old female patient admitted for gastroscopy because of epigastric pain. The antral biopsies showed dense lymphocytic infiltrates, partially forming follicles with widened marginal zones and monocytoid cells. Multiple lymphoepithelial lesions (LEL) were also observed. A MZL of the MALT type was suspected morphologically. Immunohistochemical analysis revealed the lymphatic infiltrates to be CD20, bcl-2, bcl-6 and CD10 positive, and negative for CD43, CD5 and cyclin D1. PCR-based analysis showed a JH/bcl-2 rearrangement, corresponding to the translocation t(14;18). An extranodal FL mimicking MZL was diagnosed. The present case is remarkable, as it demonstrates that the detection of LEL and monocytoid B-cells, although suggestive for MZL, is not entirely specific and can also be observed in FL. Pathologists should be aware of this diagnostic pitfall in classifying gastric B-NHL. In equivocal cases, a careful morphological examination, supported by specific immunohistochemical and molecular findings, should lead to the correct diagnosis.
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PMID:Primary gastric follicular lymphoma with parafollicular monocytoid B-cells and lymphoepithelial lesions, mimicking extranodal marginal zone lymphoma of MALT. 1246 20

Follicular lymphoma (FL) is defined as a neoplastic proliferation of follicle center cells with varying follicular areas. To learn the time trend of FL in the Osaka area, an adult T-cell leukemia/lymphoma (ATL) nonendemic area of Japan, we examined the frequency of FL among all non-Hodgkin's lymphomas (NHLs) during the period 1964 to 1987 (n = 1,000) and 1999 to 2001 (n = 659). The frequency of FL with varying follicular areas increased from 1964-1987 to 1999-2001. There was a significant difference in frequency of total cases of FL (14.2% versus 18.8%) (P < .05) and FL with no to 25% follicular area (2.3% versus 5.0%) (P < .01). According to the Berard criteria, cytologic grade of FL was defined by counting the number of centroblasts (CB) in 10 neoplastic follicles as follow: < or = 5 CB per high power field (HPF), grade 1; 6-15 CB, grade 2; >15 CB, grade 3. Immunohistochemical staining with monoclonal antibodies for bcl-2 and CD10 was performed. There was an inverse correlation between follicular area and cytological grade (P < .0001) and bcl-2 expression and cytological grade (P < .01). That is, the larger the follicular area in cases with a lower cytological grade, the stronger was bcl-2 expression in a lower cytological grade. There was a significant correlation between follicular area and stage of disease (P < .05). That is, the follicular area was larger in cases in an advanced stage. This study showed the increase in frequency of FL in Osaka, Japan. Change of lifestyle in Japan may be one of the causative factors for the increase.
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PMID:Follicular lymphoma in Osaka, Japan: histological features and chronological change. 1246 96

The expression of bcl-2, CD10, and CD20 was examined by multicolor flow cytometry in 78 samples including lymph node or other tissue biopsy specimens containing follicular lymphoma (FL; n = 17), reactive hyperplasia (RH; n = 28), or other malignant lymphomas (n = 20), as well as bone marrow aspirates (n = 13). The presence of CD10+ cells with high bcl-2 expression predicted the presence of FL rather than RH with a positive predictive value of 100% and negative predictive value of 96%. CD10+ cells with high bcl-2 expression also were found in a subset of diffuse large B-cell lymphomas and were otherwise rare in other types of malignant lymphoma. In contrast with immunohistochemical studies, a reduced but apparently measurable level of bcl-2 was present in benign follicular center cells. Hematogones showed lower bcl-2 levels than did FL cells in the bone marrow, and neutrophils were bcl-2-. Measurement of bcl-2 expression levels by multiparameter flow cytometry offers a rapid, quantitative assessment that may assist in the diagnosis of FL in lymph nodes or bone marrow, even when other CD10+ cells or admixed normal B cells are present.
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PMID:bcl-2 expression by multicolor flow cytometric analysis assists in the diagnosis of follicular lymphoma in lymph node and bone marrow. 1252 Jul 10

Discordant bone marrow (BM) involvement in patients with a diagnosis of large-cell non-Hodgkin's lymphoma (NHL) is characterized by marrow infiltrates predominantly composed of small lymphoid cell, cytologically compatible with low-grade NHL. Although this phenomenon is well described morphologically, molecular data concerning the relationship of the two lesions are lacking. The aim of the study was to investigate the clonal relationship of discordant lymphoma manifestations by using immunoglobulin heavy chain gene (IgH), as well as bcl-2 rearrangements, as molecular markers. IgH rearrangements were amplified by PCR with consensus primers directed against framework regions 3 or 2 (FR3 and FR2), followed by automated fragment length analysis and sequencing in selected cases. Rearrangements of the bcl-2 gene were identified with primers against the major breakpoint region. Small BM infiltrates were isolated by laser capture microdissection. In addition, immunohistochemistry was performed on paraffin sections using antibodies against CD3, CD10, CD20, bcl-2, bcl-6, p53, and the Ki67 antigen. Paraffin-embedded tissues of 21 cases diagnosed as diffuse large B-cell lymphoma (DLBCL) with discordant BM involvement and no previous history of low-grade B-cell NHL were analyzed. After review of immunohistochemical stains, 5 cases were excluded either as concordant BM infiltrates by large-cell lymphoma with abundant reactive T-cells (2 cases) or as benign, reactive lymphoid infiltrates (3 cases), as confirmed by a polyclonal pattern in the IgH analysis. Of the remaining 16 cases, a common clonal origin was confirmed in 8 cases by the presence of an identical clonal IgH rearrangement or bcl-2 rearrangement. In 4 cases, identification of distinct IgH or bcl-2 rearrangements gave evidence for the presence of two clonally unrelated neoplasms. The remaining 4 cases were not evaluable for technical reasons. Morphological, phenotypical, and molecular findings were compatible with a lymphoma of germinal center origin in the majority of cases. However, in 4 cases, flow cytometric analysis of the BM infiltrates revealed a B-cell chronic lymphocytic leukemia phenotype. Two of these cases were clonally related to the DLBCL and thus represented Richter's transformation. In summary, discordant BM infiltrates in DLBCL represent a heterogeneous group of disorders, encompassing cases with a clonally related, clinically occult small-cell component, as well as cases with two clonally distinct, unrelated B-cell neoplasms presenting synchronously at different locations.
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PMID:Discordant bone marrow involvement in diffuse large B-cell lymphoma: comparative molecular analysis reveals a heterogeneous group of disorders. 1253 91


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