scholarly journals Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1α (HIF-1α)

Oncogene ◽  
2003 ◽  
Vol 22 (55) ◽  
pp. 8948-8951 ◽  
Author(s):  
Reinhard Bos ◽  
Paul J van Diest ◽  
Petra van der Groep ◽  
Astrid E Greijer ◽  
Mario A J A Hermsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
B Cell ◽  
Cyclin D1 ◽  
Invasive Breast Cancer ◽  
Cell Lymphoma ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Hypoxia Inducible Factor 1Α

scholarly journals Hypoxia-Inducible Factor-1 α Expression Predicts Superior Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP

2010 ◽  
Vol 28 (6) ◽  
pp. 1017-1024 ◽  
Author(s):  
Andrew M. Evens ◽  
Laurie H. Sehn ◽  
Pedro Farinha ◽  
Beverly P. Nelson ◽  
Adekunle Raji ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Wide Range ◽  
Large B Cell

Purpose Hypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1α in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated. Patients and Methods We studied the immunohistochemical protein expression of HIF-1α on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome. Results Median follow-up for all patients was 80 months. Among all patients, HIF-1α was expressed in 62% of germinal center and 59% of non–germinal center patients. With HIF-1α analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1α protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1α–positive patients was 71% v 43% for HIF-1α–negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1α remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1α correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1α and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2). Conclusion The expression of HIF-1α protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP.

B-Cell lymphoma 2 Protein Expression and Established Clinicopathologic Features in Breast Cancers

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S51-S51
Author(s):  
Yan Xiang ◽  
Li Li ◽  
Mark Zarella ◽  
Katarzyna Brzezinska ◽  
Kareem Hosny ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
B Cell ◽  
Tumor Size ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Breast Cancers ◽  
Clinicopathologic Features ◽  
Ki 67

Abstract Objectives B-cell lymphoma 2 (Bcl-2) proto-oncogene alterations are involved in tumor genesis and play a vital role in regulating cell apoptosis. The objective of this research is to determine the prognostic value of quantitative expression of the Bcl-2 protein in breast cancer. Methods This study investigated a series of 158 primary breast cancers for Bcl-2 protein expression. Results were correlated with clinicopathologic features (age, tumor size, tubule formation, nuclear pleomorphism, mitotic count, and Nottingham prognostic index: NPI) and a panel of markers of established or presumed predictive values. Results Bcl-2 H-score (multiplied by staining intensity and percentage of positive cells) was observed to have a significant reversed correlation with the Magee Equation 1, 2, 3 (P1 < .001, P2 < .001, P3 < .001, r1 = –0.36, r2 = –0.34, r3 = –0.34). High proliferative activity as assessed by Ki-67 (>25%) staining negatively associated with Bcl-2 H-score (P = .03). Low Bcl-2 H-score was associated with old age (age >63, P = .039). Bcl-2 cytoplasm percent positive score was negatively associated (P = .02, n = 92) with overexpression of p53 (positive percentage >1.5). High Bcl-2 H-score was also associated with tumor size (T >1.5 cm, P = .034), but there was no significant correlation observed between Bcl-2 expression and the NPI calculated using the size of the lesion, the number of involved lymph nodes, and the grade of the tumor (NPI >3.4, P = .317). Conclusion (1) This study reports a correlation between Bcl-2 H-score and all three Magee equation values. (2) Bcl-2 H-score provides prognostic value better than percentage of positive cells. (3) This study further reports a correlation between Bcl-2 H-score and age, tumor size, Ki-67, and p53, irrespective of the type of adjuvant therapy received and across molecular subtypes. Collectively, these results establish the rationale for introduction of semiquantitative expression of the Bcl-2 protein to improve prognostic stratification of breast cancer patients.

BCL2 protein expression parallels its mRNA level in normal and malignant B cells

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2936-2939 ◽  
Author(s):  
Yulei Shen ◽  
Javeed Iqbal ◽  
James Z. Huang ◽  
Guimei Zhou ◽  
Wing C. Chan
Keyword(s):  
B Cells ◽  
Protein Expression ◽  
B Cell ◽  
Posttranscriptional Regulation ◽  
Cell Lymphoma ◽  
Dominant Role ◽  
Mrna Level ◽  
B Cell Lymphoma ◽  
Transcriptional Level ◽  
Bcl2 Protein

Abstract The regulation of B-cell lymphoma 2 (BCL2) protein expression in germinal center (GC) B cells has been controversial. Previous reports have indicated posttranscriptional regulation plays a dominant role. However, a number of recent studies contradicted these reports. Using real-time polymerase chain reaction (PCR) and Standardized Reverse Transcriptase-PCR (StaRT-PCR), we measured the level of mRNA expression in GC, mantle zone (MNZ), and marginal zone (MGZ) cells from laser capture microdissection. Both quantitative RT-PCR measurements of microdissected GC cells from tonsils showed that GC cells had low expression of BCL2 transcripts commensurate with the low protein expression level. These results are in agreement with microarray studies on fluorescence-activated cell sorter (FACS)-sorted cells and microdissected GC cells. We also examined BCL2 mRNA and protein expression on a series of 30 cases of diffuse large B-cell lymphoma (DLBCL) and found, in general, a good correlation. The results suggested that BCL2 protein expression is regulated at the transcriptional level in normal B cells and in the neoplastic cells in most B-cell lymphoproliferative disorders.

scholarly journals Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

2012 ◽  
Vol 30 (28) ◽  
pp. 3452-3459 ◽  
Author(s):  
Nathalie A. Johnson ◽  
Graham W. Slack ◽  
Kerry J. Savage ◽  
Joseph M. Connors ◽  
Susana Ben-Neriah ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
Large B Cell

Purpose Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. Patients and Methods We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

scholarly journals C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

2021 ◽  
Vol 6 (1) ◽  
pp. 15-20
Author(s):  
Mahmoud Tag El-Hussien ◽  
Nadia Mokhtar ◽  
Eman Naguib Khorshed
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Statistical Prediction ◽  
Proliferative Index ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Objective: To evaluate the status of C-MYC protein expression and Ki-67 proliferative index and to clarify their role in predicting relapse of diffuse large B cell lymphoma (DLBL). Materials and Methods: A retrospective study conducted on 50 cases diagnosed as DLBL in a 3 years’ time period from January 2014 till December 2016, collected from the archive of Pathology Departments of the National Cancer Institute Cairo - Egypt, Misr University for Science and Technology and private labs of authors. The diagnosis of DLBL for all cases, both nodal and extranodal, was confirmed by histopathologic examination and immunophenotyping. Automated immunohistochemical staining using antibodies against C-MYC protein and MIB-1 was used to evaluate the C-MYC expression in tumor cells and to assess their proliferative ability by calculating Ki-67 labelling index. The relation between the percentage of C-MYC protein expression, Ki-67 proliferative index, clinical data and the relapse status during the follow up period were analyzed. Results: A total of 50 cases of DLBL in both nodal and extra-nodal sites were included. Twenty-three cases (46%) were expressing the C-MYC protein, and 29 cases (58%) showed high Ki-67 proliferative index. Twenty-two cases (44%) relapsed during the follow-up period. Positive C-MYC protein expression was significantly associated with high Ki-67 proliferative index. C-MYC protein expression and high Ki-67 proliferative index were independently associated with disease relapses in 81.8% and 86.4% of cases respectively. Cases with combined C-MYC protein expression and high Ki-67 proliferative index showed statistical prediction of relapse in 81.8% of cases. Conclusion: C-MYC protein expression and high Ki-67 proliferative index were independently associated with relapse of diffuse large B cell lymphoma. Furthermore, the combined positive C-MYC protein expression and high Ki-67 proliferative index is better than a single positive test in predicting relapses among DLBL patients.

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