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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary non-Hodgkin's lymphomas of bone (PNHLB) is a rare form of extranodal lymphoma. Many studies have reported the clinical, radiologic, and histopathologic characteristics of PNHLB; however, their molecular features have not been well studied. In this report, we present the immunophenotypic and molecular characteristics of 20 primary large B-cell lymphoma (PLBCL) of bone from 20 adults. Most demonstrated centroblastic morphology, with the majority exhibiting nuclear multilobation. One case (5%) demonstrated anaplastic features with strong CD30 expression but was ALK-1 negative. BCL-6 expression was seen in 6 of 20 cases, and strong p53 protein expression was seen in 11 of 20 (55%) cases. The majority of cases analyzed (13/18 = 72%) demonstrated a clonal B-cell process by IgH gene rearrangement studies. Of the five cases that did not demonstrate a clonal population, two expressed BCL-6 protein. No cases demonstrated a bcl-2/JH rearrangement, but BCL-2 protein expression was seen in 11 of 20 (55%) cases. In summary, primary lymphoma of bone is largely a non-Hodgkin's lymphoma of large B-cell type. Our studies demonstrate that p53 and BCL-2 expression may play a role in the pathogenesis of PLCBL of bone. In addition, a subset of the cases are of putative germinal center B-cell origin based on the expression of BCL-6 protein and may be genetically distinct from follicle center lymphomas. The results provide evidence for molecular heterogeneity within primary large B-cell lymphomas of bone.
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PMID:An immunophenotypic and molecular study of primary large B-cell lymphoma of bone. 1159 70

Peripheral T-cell lymphomas (PTCL) are usually characterized by aggressive clinical behaviour and poor clinical outcome, but their biological background has not been extensively investigated to date, due to their low incidence, about 10% of all non-Hodgkin's lymphoma cases in Western countries, and also to the paucity of specific molecular-genetic abnormalities. Neverthless, there is increasing biological and clinical evidence that primary nodal PTCL should be considered separately from extra-nodal cases, but little is known about biological factors of possible clinical and prognostic impact. This immunohistochemical study has analysed the expression of p53, Mdm2, p21(WAF1), BCL-2 and p-glycoprotein (MDR-1 gene product) in a series of 45 cases of nodal peripheral T-cell lymphomas (PTCL) with 'high-grade' histology. The immunohistochemical findings were then correlated with proliferative activity and clinical outcome. p53 was over-expressed in 13 cases (28.9%). p53 positive cases showed significantly higher proliferative activity (p<0.01), more frequent expression of Bcl-2 (p<0.01) and less frequent expression of p21(WAF1) than p53 negative cases. Mdm2 and p-glycoprotein were expressed in 4/13 (30.8%) and 8/13 (61.5%) p53 positive cases respectively, and in none (0%) of the p53 negative cases (p<0.01). Analysis of the survival curves showed that p53 positive cases were associated with a significantly poorer clinical outcome than p53 negative cases, in terms of both overall survival (p=0.0032) and event-free survival (p=0.0004). Furthermore, multivariate analysis showed that p53 expression was the most important independent prognostic variable. These findings indicate that p53 over-expression identifies a subset of nodal PTCL cases with a distinctive biological profile (higher proliferative activity, less frequent expression of p21(WAF1) and more frequent expression of Bcl-2, Mdm2 and p-glycoprotein than p53 negative cases) and poor clinical outcome. The immunohistochemical analysis of p53 expression is a simple, rapid and low-cost method which may provide information of potential clinical and prognostic value in nodal peripheral T-cell lymphomas.
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PMID:p53 over-expression identifies a subset of nodal peripheral T-cell lymphomas with a distinctive biological profile and poor clinical outcome. 1167 35

We analyzed 104 patients with non-Hodgkin's lymphoma, follicular or diffuse large-B-cell-type lymphoma, in order to evaluate the correlation between clinical characteristics and immunohistochemical parameters. Immunostaining was performed by means of monoclonal antibodies against Ki-67, bcl-2, and p53 expression. Forty-nine of the patients showed follicular lymphoma. A high expression of bcl-2 was found in 93%, high expression of p53 in 57%, and low expression of Ki-67 in 96%. Follicular lymphoma grade III showed a p53 expression (p = 0.07) slightly higher than follicular lymphoma grades I and II, not reaching statistical significance. Follicular lymphoma grades I and II tended to express lower Ki-67 and higher levels of bcl-2 expression than grade III (p = 0.06). Fifty-five cases showed diffuse large-B-cell lymphoma. Among them, bcl-2 was absent in 39%, whereas p53 and Ki-67 expression were high in 38%. In the diffuse large-B-cell lymphomas, a high bcl-2 expression correlated with stages III and IV (p = 0.03) and involvement of more than one extranodal area (p = 0.03). High Ki-67 expression was also associated to extranodal involvement of more than one area (p = 0.03). Overall survival of patients did not show statistically significant differences regarding Ki-67, bcl-2, and p53 tumoral expression. Prognostic factors for overall survival in the multivariate analysis were age (p = 0.02) and LDH (p = 0.003). Time to progression was worse among follicular lymphoma with high p53 expression than with mild/moderate p53 expression (p = 0.009).
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PMID:Prognostic significance of Ki-67 nuclear proliferative antigen, bcl-2 protein, and p53 expression in follicular and diffuse large B-cell lymphoma. 1177 65

We evaluated the expression of apoptosis-regulating proteins (p53, Bcl-2, Bax, Bak and Mcl-1) in paraffin-embedded tissues of 33 patients with diffuse large B cell non-Hodgkin's lymphoma, and assessed the relationship of these proteins to clinical outcome and response to chemotherapy. Our results showed that p53 expression was an independent immunohistochemical parameter related to a poor prognosis in these lymphomas. Bcl-2, Bax, Bak and Mcl-1 proteins, though highly expressed in almost all cases were not associated with prognosis or response to treatment.
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PMID:Apoptosis-regulating proteins and prognosis in diffuse large B cell non-Hodgkin's lymphomas. 1181 69

Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in non-Hodgkin's lymphoma, but its mechanism of action has remained unclear. BCL6 efficiently immortalizes primary mouse embryonic fibroblasts and cooperates with RAS in oncogenic transformation. BCL6 overrides the senescence response downstream of p53 through a process that requires induction of cyclin D1 expression, as cyclin D1 knockout fibroblasts are specifically resistant to BCL6 immortalization. We show that BCL6 expression also dramatically extends the replicative lifespan of primary human B cells in culture and induces cyclin D1 expression, indicating that BCL6 has a similar activity in lymphoid cells. Our results suggest that BCL6 contributes to oncogenesis by rendering cells unresponsive to antiproliferative signals from the p19(ARF)-p53 pathway.
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PMID:A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling. 1191 73

In patients (pts) with non-Hodgkin's lymphoma (NHL) under 25 years, treatment with MCP-842 protocol, a short duration intense protocol, yields worse survival in pts with lymphoblastic lymphoma (LL) compared to other high grade lymphomas. In order to identify both favourable and unfavourable subgroups in pts with T-cell LL (T-LL) with respect to relapse free survival following treatment with MCP-842 protocol, we analysed the expression of p53 and bcl-2 proteins in 22 pts with T-LL treated at the Tata Memorial Hospital, Mumbai by immunohistochemistry. p53 protein overexpression was noted in 59% cases and bcl-2 overexpression was noted in 29.4% cases. p53 expression correlated with a higher rate of relapse (p = 0.03; RR 7.9). The 5-year relapse free survival (RFS) was better in p53 negative patients compared to positive patients (70 vs 38%) (log-rank sigma = 0.04). In conclusion, in this study, overexpression of p53 protein was common in patients with T-LL. T-LL pts negative for p53 are likely to benefit from the short intense protocol--MCL-842. Bcl-2 protein overexpression was not a prognostic factor in these patients.
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PMID:Expression of P53 and bcl-2 proteins in T-cell lymphoblastic lymphoma: prognostic implications. 1199 65

To investigate the role of cyclin B1 and cdc2 in the pathogenesis and progression of malignant lymphoma, 68 cases of nodal non-Hodgkin's lymphoma were examined about the expression of cyclin B1 and cdc2 along with p53 and Ki-67 by immunohistochemical method. The correlation of their expression with various clinicopathologic findings was also analyzed. Cyclin B1 and cdc2 were diffusely expressed in 39 cases (57.4%) and 54 cases (79.4%) out of 68 cases studied, respectively. The mean labeling indices of cyclin B1 and cdc2 in malignant lymphoma were 31.9% and 68.0%, respectively. In normal lymphoid tissues, cyclin B1 and cdc2 were expressed predominantly in the germinal center with mean labeling indices of 13.9% and 28.3%, respectively. The correlation between the expression of cyclin B1 and cdc2 was noted (p=0.013). The expression of Ki-67 was correlated with that of cyclin B1 (p=0.023) and marginally correlated with that of cdc2 (p=0.056). The expression of cdc2 and p53 in complete remission group to chemotherapy was lower than that of progressive disease group (p=0.047, p=0.049). In multivariate analysis, the clinical stage alone showed significance on overall survival (p=0.049). In conclusion, cyclin B1 and cdc2 appeared to be involved in the genesis or progression of malignant lymphoma and cdc2 can be a useful marker for response to chemotherapy.
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PMID:Expression of cyclin B1 and cdc2 in nodal non-Hodgkin's lymphoma and its prognostic implications. 1206 34

Mantle cell lymphoma (MCL) is a distinct type of B-cell non-Hodgkin's lymphoma characterized by cyclin D1 overexpression and the cytogenetic abnormality, the t(11;14)(q13;q32). MCL cell lines have been difficult to establish and in vitro studies of these neoplasms are scarce. We describe the establishment and characteristics of a new MCL cell line, Mino. The cells are large, growing singly and in small clumps in vitro. By flow cytometry, the immunophenotype was compatible with MCL (i.e. CD5+CD20+CD23-FMC7+). Conventional cytogenetics showed hyperdiploidy with multiple complex karyotypic abnormalities, but no evidence of the t(11;14), proven to be present only by fluorescence in situ hybridization and polymerase chain reaction (PCR) methods. Western blots showed expression of cyclin D1 but no detectable cyclin D2 and cyclin D3; the retinoblastoma protein was predominantly phosphorylated. There was expression of tumor suppressor gene products including p53, p16(INK4a), and p21(WAF1). Sequencing of the TP53 gene revealed a mutation (codon 147(valine-->glycine)) in exon 5. Epstein Barr virus was absent. In summary, Mino is a new MCL cell line that may be useful to study the pathogenesis of MCL.
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PMID:Establishment and characterization of a new mantle cell lymphoma cell line, Mino. 1212 61

The immunohistochemical analysis of lymphoid neoplasms has led to refined classification schemes based on the profile of antigen expression and correlation with morphological, cytogenetic, molecular, and clinical features. Tissue microarrays (TMAs) are a powerful tool to rapidly characterize the phenotypic profile of a large number of samples. We show that this technique can be readily applied to the study of lymphoma by examining the expression profile of a series of 193 B-cell non-Hodgkin's lymphomas (NHLs) and 29 Hodgkin's lymphomas (HLs) using immunohistochemistry and in situ hybridization (ISH). The NHL cases were studied for the expression of commonly used markers-including CD3, CD5, CD10, CD20, CD23, CD30, CD43, Bcl-2, and cyclin D1 by immunohistochemical staining of TMAs-and these results were compared with whole sections (WS) of the same cases. We found a high degree of correlation between the results achieved with TMAs or WS (86% to 100% of cases). P53 and MIB-1 staining were studied, and the results were similar to that reported in the literature. HL cases were stained for CD20, CD30, CD15 (LeuM1), and latent membrane protein 1 expression, and ISH was performed using probes for EBER-1 and-2 transcripts. The results from HL cases on TMA sections matched exactly with those of WS. We correlated cytogenetic results with immunohistochemical stains and morphology in cases of mantle cell lymphoma [t(11;14)(q13;q32)] and follicular lymphoma [t(14;18)(q32;q24)]. This extensive expression profile of B-cell NHLs and HL tissues discloses the ability of TMAs to rapidly screen a large series of cases and represents the first report of method validation for this technique in the study of lymphoma.
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PMID:Application of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma. 1239 66

Mantle cell lymphoma (MCL) is a distinct type of B-cell non-Hodgkin's lymphoma characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. Defects in apoptosis may contribute to pathogenesis. This study evaluated the expression of the anti-apoptotic protein Mcl-1 in two MCL cell lines and five frozen MCL tumours (four small-cell, one blastoid/large-cell) using western blot analysis. Mcl-1 expression was also assessed in 36 formalin-fixed, paraffin wax-embedded MCL tumours (24 small-cell, 12 blastoid/large-cell) by immunohistochemistry. Western blot analysis revealed the expected 37 kD protein product in both MCL cell lines and in five frozen tumours, with the blastoid case having the highest expression level. Using a cut-off of >10% immunolabelled cells for Mcl-1, it was found that 12 of 36 MCL tumours were positive. Mcl-1-positive tumours had a higher frequency of blastoid/large-cell morphology (8/12 versus 4/24, p = 0.009), p53 overexpression (3/10 versus 1/23, p = 0.04), and higher Ki67 immuno-labelling (p = 0.002). It is concluded that expression of Mcl-1 in MCL is heterogeneous. A relatively high level of Mcl-1 expression correlates with high-grade morphology, a high proliferative state, and p53 overexpression.
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PMID:Expression of Mcl-1 in mantle cell lymphoma is associated with high-grade morphology, a high proliferative state, and p53 overexpression. 1247 31


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