Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The International Prognostic Index (IPI) identifies poor- and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P <.0001) and bcl-2 (R = 0.14, P =.0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R = -0.025, P =.02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk. Expression of bcl-2 in the intermediate IPI group identified a further 28% of patients with an overall survival comparable to the high IPI group. In the intermediate IPI, bcl-2(-) group, the presence of a GC phenotype improved overall survival to levels approaching the IPI low group. Following this analysis only 15% of patients failed to be assigned to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and GC phenotype into the IPI significantly improves risk stratification in DLBCL. For the 36% of high-risk patients with a 2-year overall survival of 19%, alternative treatment strategies should be considered in future trials.
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PMID:Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma. 1183 Apr 58

Correlation of standard pathomorphological prognostic parameters, primary tumor size and axillary nodal status with new prognostic factor in breast carcinoma: tumor suppressor gene p53 was analyzed. The studied sample included 65 women who underwent surgery for breast carcinoma at the Surgical Clinic of Clinical Center Banja Luka, from January 1st 1997 till January 1st 1999. Statistical data analysis was performed and correlation of prognostic factors was determined. The majority of authors in this field agree that the primary tumor size and axillary nodal status are the two most important prognostic factors. These factors are the best predictors of prognosis and survival of women who had the tumor and were operated on. Tumor markers were immunohistochemically determined in the last ten years and, according to the majority of authors, are still considered the additional or relative prognostic factors in breast carcinoma. Their prognostic value and significance increase almost daily. Most frequently determined tumor markers are bcl-2, pS2, Ki-67 and p53. There was a positive, directly proportional relationship between primary tumor size and tumor suppressor gene p53, but there was no positive correlation between the axillary nodal status and tumor suppressor gene p53. Significance of determination of new tumor markers as the prognostic factors was emphasized. These markers represent a powerful tool in the early detection and prevention of breast carcinoma.
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PMID:[Correlation of size of the primary tumor and axillary node status with the p53 tumor suppressor gene in carcinoma of the breast]. 1192 86

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

Our purpose was to determine the predictive value of tumor biologic parameters in patients with HRPBC who received HDCT with ASCT as first-line treatment. From September 1992 to May 2000, 149 stage II or III HRPBC patients were enrolled in a single-arm trial using a tandem HDCT regimen followed by ASCT. Her2/neu, p53, Ki67 and bcl-2 protein expression was studied using immunohistochemic staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA index) and tumor cell proliferation (SPF) were measured by DNA flow cytometry. The relationship between these tumor biologic parameters, on the one hand, and DFS, DDFS and OS, on the other, was analyzed. With a median follow-up of 43 months (range 7-106), p53 protein accumulation (p = 0.000004), negative combined hormone receptor status (p = 0.003) and Her2/neu overexpression (p = 0.02) were significant negative predictors of OS in univariate analysis. A poorer DFS was associated with p53 positivity (p = 0.04) and nodal ratio > or = 0.8 (p = 0.008). Poorer DDFS was associated with p53 positivity (p = 0.03). In multivariate analysis, Her2/neu overexpression (RR = 3.86, 95% CI 1.48-10.1, p = 0.006) and p53 overexpression (RR = 6.06, 95% CI 2.22-16.52, p < 0.001) proved to be independent predictors of adverse OS. p53 overexpression was the only independent predictor of DFS (RR = 2.21, 95% CI 1.07-4.57, p = 0.03). p53 overexpression and Her2/neu overexpression are independent negative predictors of survival in HRPBC treated with HDCT. The adverse impact of these biologic features was probably not altered by HDCT. For HRPBC patients with tumors not overexpressing Her2/neu or p53, HDCT may be an appropriate approach to achieve long-term survival and tumor control.
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PMID:P53 is the strongest predictor of survival in high-risk primary breast cancer patients undergoing high-dose chemotherapy with autologous blood stem cell support. 1211 43

Deregulation of oncogenes and tumor suppressor genes involved in apoptosis has been associated with tumor development and progression. To investigate the involvement of apoptosis regulating proteins in oral cancer in Indian patients, primarily associated with chewing tobacco habits, immunohistochemical expression of bcl-2 and bax was examined in 63 oral squamous cell carcinomas, and 31 putative premalignant lesions. Our studies revealed overexpression of tumor specific cytoplasmic bcl-2 in 56% and bax in 43% oral cancers. The oral cancers in the Indian patients are preceded by premalignant oral lesions; hence oral lesions were examined for bcl-2 and bax expression. We observed aberrant expression of bcl-2 in 16% oral lesions comprising leukoplakias and SMF and bax in 55% oral lesions. We have already reported, p53 expression in these oral cancers and lesions. It was noteworthy that 30% oral cancers demonstrated a p53+bcl2+ pattern, and 14% samples exhibited p53+bcl2+bax+ pattern. However, none of the oral lesions showed concurrent deregulation of p53 and bcl-2 or all the three genes. Interestingly 45% oral lesions were p53-bax+ as compared to 18% oral cancers; while 39% oral lesions were bcl2-bax+ as compared to 14% oral cancers, indicating overexpression of bax in oral lesions, in the absence of p53 and bcl-2 proteins. Significant correlation was observed between positive nodal status and bcl2+ (p=0.047) and p53+bcl-2+ (p=0.01) in oral cancers. Kaplan Meier survival analysis showed significantly (p=0.059) higher survival in patients with p53- oral tumors than with p53+ tumors. Our studies thus indicate frequent overexpression of apoptosis regulators bcl-2, bax and p53 proteins in oral cancers, and a subset of oral lesions, representing early events in oral car-cinogenesis. The aberrant bcl-2 expression and loss of p53 function observed, may play an important role in the tumorigenesis of oral cancers by allowing escape from apoptosis and enabling additional genetic alterations to accrue.
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PMID:Expression of bcl-2 and bax in chewing tobacco-induced oral cancers and oral lesions from India. 1217 74

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

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

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

Esophageal adenocarcinoma arising on a background of Barrett's esophagus is increasing in incidence. A molecular understanding of both the progression of Barrett's esophagus and the factors determining the response of adenocarcinoma to neoadjuvant therapy is required, and this study focused on the role of proteins regulated by the bcl-2 family of genes, which are important regulators of programmed cell death (apoptosis). In total, 48 patients (36 men, 12 women) with Barrett's adenocarcinoma were studied. All patients received preoperative chemoradiotherapy followed by surgery. Bcl-2, bax and bcl-x protein expression were detected by standard avidin-biotin peroxidase method. Bcl-2, bax and bcl-x expression were detected in 84%, 80%, and 76%, respectively, of normal squamous mucosa. An increasing degree of dysplasia in Barrett's mucosa both before and after chemoradiotherapy was significantly associated with a reduction of bcl-2 expression (P = 0.03 and 0.009, respectively). Bcl-2 expression was significantly associated with tumor differentiation (P = 0.03) and a trend towards earlier T stage (P = 0.08), but not with nodal status. Pre-therapeutic bcl-2, bax and bcl-x protein expression (27%, 75%, and 87.5%, respectively) were not associated with tumor response or resistance to therapy. Bcl-2-positive patients had a significantly improved survival compared with bcl-2-negative tumors. A significant reduction of bcl-2 expression is associated with the progression of Barrett's mucosa to adenocarcinoma. Bcl-2 expression was associated with improved survival. Preoperative chemoradiotherapy induces expression of bax and bcl-x protein. The pretreatment expression of bcl-2 and related proteins did not predict response or resistance to neoadjuvant chemoradiotherapy, suggesting that regulators of apoptosis alone do not determine the response of Barrett's adenocarcinoma to neoadjuvant therapy.
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PMID:Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation. 1258 Dec 49

Although primary cutaneous diffuse large B-cell lymphomas (DLBCLs) except for those of the leg are grouped together with primary cutaneous follicle center cell lymphoma in the European Organization for Research and Treatment of Cancer classification of primary cutaneous lymphomas, they typically lack the usual phenotypic profile of follicular lymphoma. Whether they are truly of follicular center cell origin, have a molecular pathogenesis similar to nodal follicular lymphoma, or have any biologic features that distinguish them from secondary DLBCL involving skin remains uncertain. To address these issues, a retrospective multiparameter study of 25 patients including clinical, histologic, immunophenotypic, and cytogenetic analyses was performed. A classic CD10+, bcl-6+ follicular center cell profile was found in 10 (40%) cutaneous DLBCL (2 of 11 primary, 5 of 8 secondary, 3 of 6 unclassified) with bcl-2 expression seen only in the nonprimary cases. Of the remaining cases, 14 cases (56%) were CD10-, bcl-6+, bcl-2+/- (9 primary) and one case (4%) was CD10-, bcl-6-, bcl-2+ (0 primary). Fluorescence in situ hybridization analysis showed a t(14;18) in 0 of 9 primary and 3 of 5 secondary cases. Primary cases were frequently found in the head/neck region, whereas secondary cases were more common on the trunk and extremities. Patients with primary disease were all alive, usually having received only local therapy, at a median follow-up of 19 months. Most secondary cases were treated with chemotherapy with only one untreated patient dead of disease at a median follow-up of 5 months. Primary cutaneous DLBCLs therefore appear to be distinctive as they have fewer features of follicular lymphoma than do secondary cases. Nevertheless, some appear to be of follicular center cell origin, even though they probably have a different molecular pathogenesis than most nodal follicular lymphomas.
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PMID:Primary and secondary cutaneous diffuse large B-cell lymphomas: a multiparameter analysis of 25 cases including fluorescence in situ hybridization for t(14;18) translocation. 1260 92


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