Expressions and significance of bcl-6 and Ki-67 in diffuse large B-cell lymphoma
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Objective To study the expressions and significance of bcl-6 and Ki-67 in diffuse large B-cell lymphoma(DLBCL).Methods Immunohistochemistry technique was used to detect the expressions of bcl-6 and Ki-67 in the tissues of 90 DLBCL patients. 20 cases of reactive hyperplasia of lymph node (RH) were used as control. Results Positive expression rate of bcl-6 are 54.44 ％(49/90), 15.00 ％(3/20) in DLBCL or RH tissues respectively (x2=10.214,P=0.001). There were correlations between bcl-6 expression and Ann Arbor clinical stage, LDH, B symptoms, or Hans classification (x2=5.257,5.257,4.704,16.024 respectively,all P＜0.05).The high expression rate of Ki-67 were 80.00 ％(72/90),20.00 ％(4/20)in DLBCL or RH tissues respectively (x2=27.585,P=0.000). There were correlations between Ki-67 expression and Ann Arbor clinical stage,IPI or recent effect (x2=5.889,6.451,6.024 respectively,all P＜0.05).Conclusion There are significant correlations between the aberrant expression of bcl-6 or Ki-67 and Ann Arbor clinical stage,IPI or Hans classification. The expressions of bcl-6 and Ki-67 may provide important information for the clinical therapy and prognosis of DLBCL.
Key words:
Lymphoma, large B-cell, diffuse; bcl-6; Ki-67; ImmunohistochemistryKeywords:
Ki-67
Clinical Significance
B symptoms
The aim of this study was to assess the clinical significance and potential prognostic value of the expression of a panel of surface markers, proliferating, suppressor and oncogenic proteins in diffuse large B-cell lymphomas (DLBCL). Biopsies were collected from 158 patients with DLBCL and analyzed immunohistochemically for p53, p21/WAF1, bcl-2, cyclin-D1, bcl-6, mdr, CD5, CD30, epithelial membrane antigen (EMA), Ki-67 and c-myc positive tumor cells. Among these, 76 young and middle-aged patients (20-65 years) were selected to investigate the relationship between protein expression, clinical features, and survival. Survival analysis showed that advanced stage, high lactic dehydrogenase level, and high International Prognostic Index (IPI) were poor prognostic factors associated with a shorter overall survival (OS) and disease-free survival (DFS) times. A high p53 expression and low bcl-6 expression were associated with a shorter DFS time. The histological variant type, cyclin-D1+ CD5+ DLBCL, positive epithelial membrane antigen (EMA+) CD30- DLBCL, high bcl-2 expression, and low Ki-67 proliferation activity tended to be associated with worse survival, but the correlations were not statistically significant. In the multivariate analysis, the most significant factors were age, followed by IPI and last p53. The expression of p21/WAF1, mdr, and c-myc proteins did not influence OS and DFS. The expression of p53 and bcl-6 proteins may be useful prognostic indicators in DLBCL. Cyclin-D1+ CD5+ or EMA+ CD30- DLBCL tended to predict a worse survival and may probably bear a significant prognostic value worthy of consideration. Overall, clinical factors appeared to be more important than biologic parameters in determining the prognosis of diffuse large B-cell lymphomas.
CD5
International Prognostic Index
B symptoms
BCL10
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Objective To evaluate the expression of proliferative antigen Ki 67 and apoptosis antagonizing protein Bcl 2 as well as their clinical significance in non Hodgkin′s lymphoma(NHL).Methods Ki 67 antigen and Bcl 2 protein were measured by immunohistochemistry on paraffin embedded slices in 35 cases of NHL.Results (1)The level of Ki 67 expression in low grade NHL was lower than that in high grade NHL( P 0.01),while Bcl 2 expression in lower grade NHL was higher than that in high grade( P 0.01).(2) The level of Bcl 2 expression in B cell NHL was higher than that in T cell NHL( P 0.02),but there was no difference in the expression of Ki 67.(3)The level of Bcl 2 expression in remission group was lower than that in non remission group after the first course of chemotherapy, but there was no significant difference in Ki 67 expression.(4)The survival time was longer in the group with Ki 67≤20% than that in the group with Ki 67 20%, but there was no significant difference of survival time between the high and low expresion group of Bcl 2.Conclusions The level of Ki 67 and Bcl 2 expression was closely related with the grade of malignant and the prognosis of NHL. They were a pair of useful markers for understanding the generation and prognosis of NHL.
Ki-67
Clinical Significance
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BCL6
Activation-induced (cytidine) deaminase
Tissue microarray
Immunophenotyping
Ki-67
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Objective:To study the expression of survivin, bcl-2 and Ki-67 proteins and analyze their prognostic significance for chemotherapy insensitivity and recurrence of diffuse large B cell lymphomas (DLBCL). Methods: Forty-one patients with DLBCL confirmed by pathological examination between 2000 and 2003 in our hospital were recruited in this study. The correlation analysis was performed between international prognostic index and prognosis. The specimen was collected from 20 patients. The expressions of survivin, bcl-2, and Ki-67 proteins was tested by immunohistochemical (IHC) method and correlated with survival rate. Results: Univariate analysis showed that clinical stage, extranodal invasion, ECOG performance status, LDH level, and clinical efficacy were independent prognostic factors for progression-free survival (PFS). Combined treatment with radiotherapy and rituxan had no influence on prognosis. Multivariate analysis indicated ECOG performance status and clinical efficacy were independent prognostic factors for PFS. Immunohistochemical analysis demonstrated patients with high Ki-67 index had shorter survival time (P0. 05). The recurrence group had higher Ki-67 index and bcl-2 expression (P0. 05 and P = 0. 069). The mortality rate was higher in patients with increased bcl-2 expression (P0. 05). The survival time had the tendency to be short in the patients with survivin nuclear translocation than those without nuclear translocation, but the difference was not significant (P0. 05). Conclusion:Clinical stage, extranodal invasion, ECOG performance status, LDH level, clinical efficacy, and Ki-67 are independent prognostic factors for DLBCL. High Ki-67 index was a risk factor for recurrence and high bcl-2 expression was a risk factor for prognosis. Nuclear positivity of survivin indicated poor prognosis.
Survivin
International Prognostic Index
Univariate analysis
Clinical Significance
Ki-67
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Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphatic neoplasm, accounting for about 30–40% of non-Hodgkin’s lymphoma cases. Objectives: DLBCL is a progressive disease with clinical, genetic and molecular heterogeneity. The prognostic value of B-cell lymphoma 2 (BCL2) and Ki-67 in DLBCL patients has been controversial. Patients and Methods: In this study, we investigated the correlation of BCL2 and Ki-67 expression with clinical features such as age, gender, B symptoms and lactate dehydrogenase (LDH) levels, subtypes of DLBCL, its staging and prognosis in 36 cases of DLBCL. The expression of BCL2 and Ki-67 was measured by immunohistochemistry. Results: There was no significant correlation between BCL2 expression and staging (P=0.082), however Ki-67 expression had a significant correlation with staging (P=0.002). There was no statistically significant correlation between BCL2 and Ki-67 with prognosis of the disease. We found a significant correlation between the germinal center B-cell (GCB) and non- GCB subtypes with BCL2 expression (P=0.024), since patients with non- GCB subtype had a higher BCL2 expression. Our study also demonstrated a significant relationship between BCL2 and Ki-67 expression, therefore, with the increase of the expression of a marker, another increases (P=0.045). Conclusion: BCL2 and Ki-67 expressions were not associated with prognosis. Overexpression of Ki-67 was associated with higher clinical stages. BCL2 expression is higher in non-GCB subtype of DLBCL. Therefore, our study shows that the subsequent studies of BCL2 and other biomarkers in the DLBCL should be based on the DLBCL subtypes.
Ki-67
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Objective: To investigate the relationship between the protein expression of C-MYC, bcl-2 and bcl-6 and the clinicopathological characteristics in patients with de novo CD5-positive diffuse large B cell lymphoma (CD5(+)DLBCL). Methods: Fifty seven cases of de novo CD5(+)DLBCL were collected at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2013 to September 2018. The hematoxylin-eosin stained slides were reviewed, and immunohistochemical (IHC) staining and FISH were used to analyze the relationship between C-MYC, bcl-2, bcl-6 expression and the clinicopathologic characteristics of patients. Results: Among these 57 cases, 27 were male and 30 were female. The age of onset was 35-99 years old. The IHC expression rates of C-MYC, bcl-2 and bcl-6 were 50.9% (29/57), 84.2% (48/57), and 75.4% (43/57) respectively; and co-expression rate of C-MYC and bcl-2 proteins was 40.4 (23/57). There was no significant correlation between protein expression and patients' genders, clinical stage, the level of serum LDH,β2 microglobulin, IPI,B symptoms, bone marrow involvement and central nervous system recurrence (P>0.05). Univariate analysis showed that the median OS of C-MYC negative patients was significantly longer than C-MYC positive patients (P<0.05); and the median OS of patients without double expression was significantly longer than that of patients with positive expression (P<0.05), and bcl-6 positive patients had longer median OS than bcl-6 negative patients (P<0.05). There was no significant correlation between prognosis and bcl-2 protein expression (P>0.05) . Cox multivariate analysis showed C-MYC protein expression was an independent predictor of OS in de novo CD5(+)DLBCL (P<0.05). Conclusions: Bcl-2 protein expression has no effect on the prognosis in de novo CD5(+)DLBCL whereas bcl-6 expression is correlated with good prognosis. C-MYC protein expression could be used as an independent and effective index to predict the prognosis of patients with de novo CD5(+)DLBCL.However, the relationship between protein expression and gene rearrangement of C-MYC, bcl-2 and bcl-6 needs to be further explored.目的： 探讨C-MYC、bcl-2、bcl-6蛋白的表达与原发性CD5阳性的弥漫性大B细胞淋巴瘤（CD5-positive diffuse large B cell lymphoma，CD5(+)DLBCL）患者临床病理特征之间的关系。 方法： 收集2013年2月至2018年9月上海交通大学医学院附属瑞金医院初治诊断为原发性CD5(+)DLBCL标本57例，采用HE染色、免疫组织化学技术及荧光原位杂交（FISH）法，检测原发性CD5(+)DLBCL中C-MYC、bcl-2、bcl-6蛋白的表达情况，并分析其与临床病理特征之间的关系。 结果： 57例原发性CD5(+)DLBCL中，男性27例，女性30例，发病年龄35~99岁。C-MYC、bcl-2、bcl-6蛋白表达阳性率分别为50.9%（29/57）、84.2%（48/57）、75.4%（43/57），其中C-MYC和bcl-2双表达阳性率为40.4%（23/57）；其在患者性别、临床分期、血清乳酸脱氢酶（LDH）水平、β2微球蛋白水平、国际预后指数（IPI）评分、B症状、骨髓侵犯和中枢神经系统（CNS）复发等临床特征之间差异无统计学意义（P>0.05）；单因素生存分析显示：C-MYC阴性患者中位总生存率显著高于阳性患者（P=0.010），双表达阴性患者中位总生存率显著高于阳性患者（P=0.008），bcl-6阳性患者中位总生存率显著高于阴性患者，差异具有统计学意义（P=0.021），bcl-2蛋白表达与预后无明显相关性（P>0.05）；Cox模型多因素分析显示，C-MYC蛋白表达可作为原发性CD5(+)DLBCL患者总生存率的独立预测指标（P=0.034）。 结论： C-MYC、bcl-2、bcl-6蛋白在原发性CD5(+)DLBCL的预后价值中，bcl-2表达对预后无影响，bcl-6阳性组预后较好，C-MYC蛋白表达可作为预测原发性CD5(+)DLBCL患者预后的独立有效指标，但对于原发性CD5(+)DLBCL患者中，C-MYC、bcl-2及bcl-6蛋白的表达与C-MYC、bcl-2及bcl-6基因重排之间的关系，还有待扩大样本量进一步深入探讨。.
Univariate analysis
CD5
B symptoms
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Objective: To study the correlation of bcl 2 and ki 67 with biological behaviors and prognosis of renal cell carcinomas (RCC).Methods:The expressions of bcl 2 and ki 67 in 60 RCC and 5 normal renal tissue specimens were detected by immunohistochemical method,LSAB.Results:Positive staining of bcl-2 protein was found in 66.7% of RCC (40/60), while none in normal renal tissues. Expression of bcl 2 was closely related to the clinical stage and cell grading. The expression of bcl 2 gene was decreased with the advances of stage and grading( P 0.01). No correlation was found between bcl 2 expression and histology type.The cases with negative bcl 2 expression had a poor prognosis. Although expression of ki 67 was found in all RCC, there was a faint stain in normal renal tissue.The expression of ki 67 was closely related to the clinical stage and grading ( P 0.005). No correlation was found between ki 67 and histology type. The cases with a higher expression had poor prognosis.Conclusion:bcl 2 and ki 67 might be applicable as tumor markers for the evaluation of malignant potential and prognosis of RCC.
Grading (engineering)
Histology
Stain
Ki-67
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Background: Diffuse large B-cell lymphoma (DLBCL) is considered the commonest subtype of non-Hodgkin lymphoma (NHL) in the world.It is a refractory disease with a high mortality rate due to frequent relapses.Several prognostic parameters are now widely studied for risk stratification and achieving a better outcome.Objectives: In this study, we aim to assess the prognostic value of immunohistochemical expression of CD10, BCL6, and MUM1 independently as surrogate markers for cell of origin (COO) classification of DLBCL and their correlation with clinicopathological characters and survival.Patients and methods: This is a retrospective study conducted on 63 cases of DLBCL, NOS.Full-faced sections were constructed and immunostained for CD10, BCL6, and MUM1.Results: CD10 expression was associated with early-stage (P=0.003),normal serum LDH level (P=0.022),absence of B symptoms (P=0.019),low international prognostic index (IPI) and age-adjusted-IPI (P=0.001) and also associated with longer progression free survival (PFS) (P=0.006).BCL6 expression was associated with centroblastic variant (P=0.005),good ECOG performance status (P=0.038) and low IPI (P=0.004) and also associated with better overall survival (OS) (P=0.028) and PFS (P=0.018).MUM1 expression was associated with advanced-stage (P=0.002) while no significant association was detected with other clinicopathological parameters or survival.Conclusion CD10, BCL6, and MUM1 can be used independently as prognostic immunohistochemical markers for DLBCL that may denote the clinical behavior of the disease and further patients' outcomes.
BCL6
International Prognostic Index
Performance status
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Objective To study P16, P53 and Bcl-2 expression and Ki-67 labelling index correlations with invasiveness and prognosis in thymoma. Methods P16, P53, Bcl-2 expression and Ki-67 labelling index in 41 thymomas were examined immunohistochemically. Results P16, P53 and Bcl-2 positive rate in thymoma were 48.8%、58.5% and 41.5%, respectively. Ki-67 LI为9.55%±6.75%. P16、Bcl-2 expressions were not associated with invasiveness and prognosis of thymoma. P53 expression and Ki-67 LI correlated with the invasion of thymoma(P0.05,P0.01), moreover, Ki-67 LI correlated with the prognosis of thymoma(P0.05). Conclusion P53 expression and Ki-67 LI can help differntiate invasive thymoma. Ki-67 LI is a good indicator for prognosis of thymomas.
Ki-67
P53 expression
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Large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma among adults. In some cases, DLBCL may seem similar to carcinoma cells, presenting a round, oval, or polygonal shape and clear nuclei. We found that the expression of P63 accounted for a considerable proportion of DLBCL cases. Under the circumstances, P63 expression may lead to a misdiagnosis, especially with a small biopsy. We aim to investigate the expression status and prognostic significance of P63 in a cohort of Chinese DLBCL patients.P63, ΔNP63(P40), P53 and Ki67 were detected by immunohistochemistry (IHC). A ROC curve was adopted to find the best cut-off value for positive P63/P53 expression and high Ki67 expression. We defined P53 as positive when ≥50% of the tumor cells showed staining. The relationship between P63 and P53/Ki67 expression was examined. Time-to-event endpoints were estimated according to the Kaplan-Meier method. Moreover, multivariate analyses were conducted to evaluate the prognostic factors in DLBCL.Out of all the 159 DLBCL cases, 76 (47.8%) expressed P63 in the nuclei, while 41 (25.8%) were determined to have high expression by using a ROC cut-off value "≥6". Examination of the different P63 isoforms revealed that the ΔNP63(P40) was unclearly and weakly expressed in only 3 cases, showing a fuzzy yellow cytoplasm. P63 expression was not correlated with subtype (GCB or non-GCB) or P53 but was correlated with a high proliferative index (Ki67). Kaplan-Meier analyses revealed that P63 expression was correlated with overall survival, and P63 positive cases showed poor survival outcomes (P<0.05) in our cohort.ΔNP63(P40) is a useful marker in the differential diagnosis of poorly differentiated squamous cell carcinoma versus DLBCL in small needle biopsy. P63 may be involved in DLBCL tumor progression, and it is an unfavorable prognostic marker in DLBCL. A subgroup of P63 and P53 coexpression DLBCL patients with an extremely poor prognosis should be noted.
Single Center
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