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)

Bcl-6 (LAZ-3) and Bcl-2 gene rearrangements have been respectively reported in 20-35 per cent and 10-25 per cent of diffuse large B-cell lymphomas (DLBCLs). Although these genetic lesions have been associated with different clinical outcomes (i.e., more favourable in Bcl-6 rearranged cases and poorer in Bcl-2 rearranged cases), their prognostic significance is still controversial. In the present study, we have investigated by Southern blot analysis the Bcl-6 and Bcl-2 gene configuration in a series of 80 lymph nodes involved by well-characterized DLBCLs, histologically defined according to the REAL and the updated Kiel classifications. The molecular findings have been correlated with the clinical features at presentation and with response to therapy. The majority of cases (57/80 = 71.2 per cent) had a centroblastic morphology. Bcl-6 rearrangements were detected in 23/80 cases (28.8 per cent), and were similarly associated with centroblastic (18/57 = 31.6 per cent) or immunoblastic (3/11 = 27.3 per cent) histotypes. In contrast, Bcl-2 was found to be rearranged in only three cases of centroblastic lymphoma (3.8 per cent). No significant differences were found between Bcl-6 rearranged and germline cases, as far as the clinical features at presentation are concerned. Forty-one patients, in whom the lymph node biopsy was performed at diagnosis, could be evaluated for response to treatment and clinical outcome. Most of these cases (30/41 = 73.2 per cent) were nodal DLBCL, without extranodal site involvement. Analysis of the clinical outcome showed no statistically significant differences between Bcl-6 rearranged and Bcl-6 germline cases (actuarial overall survival 50 per cent vs. 48 per cent, event-free survival 45 per cent vs. 46 per cent, at 4 years). These findings confirm that Bcl-6 rearrangements are the most frequent genetic lesion in DLBCL. The incidence of Bcl-2 involvement in our series is significantly lower than the figures reported in other studies, mainly from North American countries, probably reflecting heterogeneous patient selection and/or epidemiological variability. Finally, our results suggest that no relevant clinical differences are observed between Bcl-6 rearranged and Bcl-6 germline cases, when nodal DLBCLs are considered.
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PMID:Pathogenetic and clinical implications of Bcl-6 and Bcl-2 gene configuration in nodal diffuse large B-cell lymphomas. 942 82

We studied overexpression of p53, Bcl-2, Bcl-6, c-Myc and Mdm2 proteins by immunohistochemistry for a total of 27 primary central nervous system B cell lymphomas (CNS lymphomas) in immunocompetent patients and one CNS lymphoma in an AIDS patient. The expression of Epstein-Barr (EB) virus-encoded small RNA-1 (EBER-1) was also analysed using in situ hybridisation. Overexpression (more than 20% of cells stained) of p53 protein was detected in 8 of 27 immunocompetent cases (30%); 6 cases showed a nuclear stain and 2 cases showed cytoplasmic stain (nuclear exclusion). Strong Bcl-2 or Bcl-6 immunoreactivity suggestive of overexpression was seen, respectively, in 5 (19%) and 6 (22%) cases; 2 cases were positive for both immunoreactivities. Interestingly, overexpression of Bcl-2 or Bcl-6 was not seen in the cases which showed p53 overexpression (P < 0.03; chi-square test). EBER-1 expression was not detected in any of the 27 immunocompetent cases, but was found in the AIDS-related CNS lymphoma, which also showed an overexpression of Bcl-6, but not Bcl-2. None of the cases showed c-Myc or Mdm2 overexpression. Taken together, it is suggested that CNS lymphoma in immunocompetent hosts is a distinct disease that has a different molecular profile from those of systemic lymphoma and/or AIDS-related CNS lymphoma.
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PMID:Expression of oncogenic molecules in primary central nervous system lymphomas in immunocompetent patients. 960 May 97

We performed a retrospective immunohistochemical study of the relationships between clinical manifestations and outcomes of diffuse large B-cell lymphoma (DLBCL) and expression of oncogenic proteins in 21 cases of DLBCL at various clinical stages. Cases of nodal origin expressed p53 more often and presented with high clinical stage more frequently than those of extranodal origin. Expression of c-Myc or p53, but not Bcl-6, Bcl-2, or Bcl-1, showed a statistically significant positive correlation with high clinical stage at presentation and with high or high-intermediate risk. Coexpression of c-Myc and p53 occurred in 7 of 12 patients with high clinical stage but was absent in patients with low clinical stage; coexpression was more frequent in patients with high or high-intermediate risk than in patients with low or low-intermediate risk. Four patients with this coexpression pattern demonstrated an unusually aggressive clinical course (median survival, 7 months). Coexpression of c-Myc and p53 seems to be a better indicator than the MIB1 proliferative index for identification of a cohort of aggressive disease in patients with DLBCL.
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PMID:Expression of c-Myc and p53 correlates with clinical outcome in diffuse large B-cell lymphomas. 1133 87

Primary cutaneous B-cell lymphomas (PCBLs) may have particular clinicopathologic characteristics distinct from their lymph node-based counterparts. It has been suggested that PCBLs should have a separate classification system. The aim of this study was to determine whether the Revised European-American Lymphoid Neoplasms (REAL) classification is applicable to PCBL. Thirty-nine cases of PCBL from 36 patients, consisting of 20 men and 16 women (median age 66 yrs), were included in this study. Paraffin-section immunohistochemistry for CD3, CD5, CD10, CD20, CD43, Bcl-2, Bcl-6, and cyclin D1 was performed in all cases. Immunostaining for immunoglobulin light chains was also performed on cases histologically diagnosed as extranodal marginal zone lymphoma (MZL) and primary cutaneous B-cell lymphoma unclassifiable (PCBLu). Polymerase chain reaction (PCR) analysis of t(14;18) was performed in all cases. Immunoglobulin heavy chain gene rearrangement (VDJ) was tested by PCR on all follicle center lymphoma (FCL), MZL, and PCBLu cases. The 39 cases consisted of 15 (39%) FCLs, 13 (33%) diffuse large B-cell lymphomas (DLCL), 9 (23%) extranodal MZL, and 2 cases of PCBLu. Anatomically, 59% of PCBLs occurred in the head and neck, of which approximately 57% were FCL. Five of six cases presenting on the lower extremity were DLCL. Follow-up data was available from all 39 patients with a mean of 50.8 months. All but two patients are alive with or without disease at last contact. One patient with DLCL died of lung metastases and the other DLCL patient died of sepsis as a complication of therapy. In all 15 cases of FCL, CD10 and/or Bcl-6 expression supported the follicle center origin of the neoplastic cells. In contrast to previous reports, we found that 53% (8 of 15) of primary cutaneous FCL had either Bcl-2 protein expression or t(14;18). Our data indicate that many cases of primary cutaneous FCL have Bcl-2 alterations similar to their nodal counterpart. We found that 95% (37 of 39) of PCBLs could be classified according to the REAL classification, supporting its applicability in cutaneous lymphomas.
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PMID:Clinicopathologic reassessment of primary cutaneous B-cell lymphomas with immunophenotypic and molecular genetic characterization. 1125 30

Diffuse large B-cell lymphomas (DLBCL) are a biologically and clinically heterogeneous entity. Although some DLBCL represent transformation of follicular lymphomas (FL), the proportion that is of follicular center cell (FCC) origin remains uncertain. Immunophenotypic and genotypic markers used to suggest a FCC origin for a lymphoma (bcl-6 and CD10 expression, lack of CD138 expression, bcl-2 rearrangements [R]) or to subdivide DLBCL (bcl-2 expression, bcl-6 R) were therefore investigated in 22 FL and 44 DLBCL using paraffin section immunostains and Southern blot/polymerase chain reaction analysis. All FL tested were bcl-6+ (19) and CD138- (22) with 16/19 also bcl-2 and CD10+ (classic phenotype), one bcl2+, CD10- (grade III) and two bcl2-, CD10+ (grade II or III). Bcl-2R was identified in 4/5 FL-GrI, 3/6 FL-GrII, and 1/3 FL-GrIII. Bcl-6R was found in 0/5, 2/4, and 0/3 FL, respectively. All but 3/41 DLBCL were bcl-6+ with 17/37 also bcl-2+ and CD10+. Three of these cases were also CD138+. Twelve bcl-6+ cases were bcl-2+, CD10-, six bcl-2-, CD10+, and two bcl-2-, CD10-. The three bcl-6- cases were bcl-2+, CD138- and two were CD10+. Bcl-2R was identified in 5/27 DLBCL with 4/5 bcl-2+, 3/4 tested CD10+ and 4/4 bcl-6+. Bcl-6R was identified in 7/26 including three with a classic FL phenotype. The vast majority of DLBCL in this study have an immunophenotype that supports a FCC origin. Although the proportion of DLBCL that co-expressed bcl-6, CD10 and bcl-2 was lower than for the FL, absence of bcl-2 or CD10 may be associated with higher grade FL It is also possible that bcl-6 expression is not completely specific for a FCC origin. Only a minority of cases suggested postfollicular differentiation. Only a minority of DLBCL show bcl-2R, suggesting that many have a different molecular pathogenesis than most low-grade FL. Bcl-6R did not exclude a FCC origin.
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PMID:Immunophenotypic and genotypic markers of follicular center cell neoplasia in diffuse large B-cell lymphomas. 1110 80

Cutaneous follicle center lymphoma (FCL) is reported to have a unique immunophenotype and clinical course as compared with nodal FCL. We studied 19 cases of FCL of the skin using paraffin embedded tissue. An immunohistochemistry panel included CD45, CD3, CD20, CD43, CD21, bcl-2, bcl-6, CD5, and CD10. Molecular studies were performed by polymerase chain reaction for immunoglobulin heavy chain (IgH) and t(14;18). Trisomy 3 was performed by fluorescent in situ hybridization (FISH) in 13 cases. Follow up was obtained in 17 cases (range 3 to 137 months). Patients included 10 females and 9 males ranging in age from 33 to 88 years at first presentation (mean, 64). Twelve of 19 presented in the head and neck and 6 in the trunk and 1 on the arm. All had no known lymph node disease at presentation. Seventeen patients had no nodal disease with a minimum 3 month follow-up; 2/19 had unknown lymph node status with no follow-up. All cases were immunoreactive with CD20 and negative with CD3. Bcl-2 was immunoreactive in 11/18 cases, bcl-6 in 15/15, CD10 in 14/17, CD43 in 2/16 (both were CD10 immunoreactive) and CD5 in 1/15 (it was also bcl-6 immunoreactive). Eight of 18 cases were monoclonal for IgH. Three of 17 showed the presence of t(14;18). FISH was positive in 4 cases for trisomy 3 ranging from 16 to 22% (12% threshold). Follow-up showed no evidence of disease in 14/17 patients (4 to 137 mos). 3/17 patients are alive with disease (17 to 100 mo), and no patients died of disease.
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PMID:Cutaneous follicle center lymphoma: a clinicopathologic study of 19 cases. 1155 77

Most follicular lymphomas (FLs) transform to diffuse lymphoma eventually, comprising a significant proportion of diffuse large B-cell lymphoma (DLBCL). Judging by bcl-2 rearrangement (bcl-2R), one third of DLBCLs are believed to be of FL derivation in the Western population. However, bcl-2R is not specific and is not detectable in every case of FL. In East Asia, FL is uncommon but DLBCL is not. The proportion of tumors of FL origin in DLBCL is not known in this region. The coexpression of Bcl-6 and CD10 proteins, a reliable marker to identify germinal center (GC) B-cell lymphoma including FL, was analyzed in primary nodal DLBCLs (n = 104) diagnosed at major hospitals in Seoul during a recent 2-year period, along with well-defined cases (n = 17) of nodal FL as controls. Bcl-2 protein expression (n = 77) was also studied along with bcl-2R (n = 64), by polymerase chain reaction. Formalin-fixed archival specimens were used in all these assays. The Bcl-6/CD10 coexpression was observed in 35 DLBCLs (34%) and 14 FLs (82%), and most of them showed a pattern of Bcl-6 expression similar to that of the GC. Bcl-2 expression or bcl-2R did not correlate with Bcl-6/CD10 coexpression. Histologically, compartmentalizing sclerosis was associated with a high rate of the coexpression (8 of 10). In conclusion, to detect GC B-cell lymphoma in routine biopsy specimens, a pattern of Bcl-6 staining similar to the GC must be identified. Bcl-6+/CD10+ GC B-cell lymphomas thus defined comprised one third of primary nodal DLBCLs in Korea. The incidence rate is similar to that in the West. The reasons for the discrepancy between the incidence of GC B-cell lymphoma and the paucity of the follicular pattern in East Asian subjects warrant further studies.
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PMID:Coexpression of Bcl-6 and CD10 in diffuse large B-cell lymphomas: significance of Bcl-6 expression patterns in identifying germinal center B-cell lymphoma. 1156 25

Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical features and having a high mortality rate. Although not specifically recognized by the Revised European-American Classification of Lymphoid Neoplasms, it likely will appear as a subtype of diffuse large B-cell lymphoma in the upcoming WHO classification. Some authors may also consider it to be a subtype of cutaneous lymphomas. Recent studies have reported an immunophenotypic heterogeneity of AL, and in rare instances, an association with other NHL. To further characterize AL, we studied the immunophenotype by immunohistochemistry for CD5, CD10, CD20, bcl-2, and bcl-6 in 18 cases of B-cell AL identified at three medical centers in North America. Bcl-2 gene rearrangement status by polymerase chain reaction and Epstein Barr virus status by in situ hybridization also were evaluated. Eight men and 10 women were identified with AL (median age 71 years). Eleven patients were diagnosed in life and seven were diagnosed at autopsy. Neurologic symptoms were the most common presentation, seen in six patients. Skin was the most commonly biopsied site. All showed classic intravascular localization; in two cases, there was also a minor diffuse large cell lymphoma component observed in some organs. Most (89%) of the cases expressed bcl-2 protein; CD10, bcl-6 and CD5 were each expressed in 22% of cases. Based on CD5 and CD10 expression, three major groups were evident: CD5-, CD10- (11 cases); CD5+, CD10- (3 cases), and CD5-, CD10+ (3 cases). Even though a follicle center lymphoma preceded the AL in one patient, we did not detect bcl-2 gene rearrangement in any of these cases. All cases were negative for Epstein Barr virus. Of the five treated with chemotherapy, two achieved a complete remission. Based on these findings, we conclude that ALs are clinically and immunophenotypically heterogeneous and may represent more than one pathogenetic entity. In some instances AL may be preceded by another lymphoproliferative disorder, raising the possibility that some cases of AL may represent a transformation from another type of lymphoma. Cutaneous manifestations of AL are common; however, it appears to be a systemic lymphoma. Although often fatal, patients with AL who are diagnosed early and treated with chemotherapy may achieve remission.
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PMID:Angiotropic lymphoma: an immunophenotypically and clinically heterogeneous lymphoma. 1170 77

Follicular lymphoma is a rare lymphoid malignancy in pediatric patients and consequently remains poorly characterized, particularly with respect to its immunophenotype and molecular pathogenesis. A total of 23 pediatric patients with follicular lymphoma were identified, with a median age of 11 years and a male-to-female ratio of 2.3:1. Of the 19 patients for whom presenting clinical features were available, 15 patients had stage I, 1 had stage II, and 3 had stage III or IV disease. All tumors had a follicular architecture, and 74% of cases had grade 2 or 3 histologic features. All patients expressed CD20 and bcl-6, and 80% were positive for CD10. Bcl-2 expression was detected in only 5 of 16 cases. Consistent with this finding, bcl-2 gene rearrangements were detected in only 2 of 16 cases by polymerase chain reaction. These patients were treated primarily with cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy; 4 patients also received involved-field irradiation. Of the 13 patients with available clinical follow-up, all but 2 achieved durable clinical remission. Importantly, all 4 patients with tumors diffusely positive for bcl-2 either presented with stage III/IV disease or had disease refractory to therapy, whereas patients with bcl-2-negative tumors uniformly had stage I disease, achieved complete remission, and experienced no relapses. These findings indicate that, in contrast to adult follicular lymphomas, dysregulated bcl-2 expression does not play a significant pathogenetic role in most pediatric follicular lymphomas. However, bcl-2 expression in pediatric follicular lymphoma identifies a subset of patients in whom disease is often disseminated at clinical presentation and is more refractory to combination chemotherapy.
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PMID:Clinicopathologic analysis of follicular lymphoma occurring in children. 1187 66

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.
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PMID:Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion. 1207 68


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