Expression And Significance Of XIAP、Survivin、Bcl-2、Caspase-3and In PCNA In B Cell Non-Hodgkin Lymphoma

Objective:Non-Hodgkin’s lymphomas(NHLs) are the most common maligancies of the hematopoietic and lymphoid tissue, epidemiological survey shows that the incidence of NHL is rising in recent years worldwide, while the treatment effect is not very satisfactory, so it is seriously harmful to human health. The key to effective treatment is how extent we know about its mechanism. A large number of studies have shown that the abnormal regulation of cell proliferation and apoptosis is the basis of tumorigenesis. In this study, We detected the expression of XIAP, Survivin, Bcl-2, Caspase-3and PCNA in B cell non-Hodgkin’s lymphoma and the lymph node with reactive hyperplasia as a control. Through this work we aim to find some possible mechanisms involved in the pathogenesis of non-Hodgkin’s lymphoma and hope what we did could provide theoretical support to the clinical molecular therapyMethods:The total50cases of B-NHLs, including41cases of diffuse large B cell lymphoma,7cases of follicular lymphoma,2cases of mantle cell lymphoma and20cases of lymph nodes with reactive hyperplasia between2008-2010are taken from the department of pathology of Tianjin General Hospital. All cases were confirmed again by pathological doctors. The expression of XIAP, Survivin, Bcl-2, Caspase-3and PCNA in B cell non-Hodgkin’s lymphoma and lymph nodes with reactive hyperplasia were detected by the two-step PV6000immunohistochemical staining method. All data were analysed by statistic software SPSS, version16.0. The method of x2test, t test and analysis of variance were used to compare the difference of each molecule between groups. The method of pearson contingency coefficine was used to analysis the correlation. P<0.05was considered statistically significant.Results:1.The XIAP protein was expressed in cytoplasm with a brownish yellow or brown granular appearance and the nucleus was not stained. In the50cases of B-NHL,29cases were positive while21cases were negative, the positive rate was58%; In the20cases of lymph nodes with reactive hyperplasia,6cases were positive while14cases were negative, the positive rate was30%. The expression of XIAP in B-NHL is higher than that in reactive hyperplasia of lymph nodes, the difference was statistically significant (χ2=4.48, P<0.05). There were no significant differences between the expression of XIAP in B-NHL and their pathological parameters of lymphoma (P>0.05).2. The Survivin protein was expressed in nucleus with a brownish yellow or tan granular appearance and the cytoplasm was not stained. In the50cases of B-NHL,40cases were positive while10cases were negative, the positive rate was80%; In the20cases of lymph nodes with reactive hyperplasia6cases were positive while14cases were negative, the positive rate was25%. The expression of Survivin in B-NHL is higher than that in lymph nodes with reactive hyperplasia, the difference was statistically significant (χ2=15.815, P<0.01). There were no significant differences between the expression of Survivin in B-NHL and their pathological parameters of lymphoma (P>0.05).3. The Bcl-2protein was expressed in cytoplasm and membrane of the cells with a brownish yellow or brown granular appearance. In the50cases of B-NHL,39cases were positive while11cases were negative, the positive rate was78%; In20cases of lymph nodes with reactive hyperplasia,7cases were positive while13cases were negative, the positive rate was35%. The expression of Bcl-2in B-NHL is higher than that in lymph nodes with reactive hyperplasia, the difference was statistically significant (χ2=14.643, P<0.01). There were no significant differences between the expression of Bcl-2in B-NHL and their pathological parameters of lymphoma (P>0.05).4. The Caspase-3protein was expressed in cytoplasm and cell membrane of the cells with a brownish yellow or brown granular appearance. In the50cases of B-NHL,30cases were positive while20cases were negative, the positive rate was60%; In the20cases of lymph nodes with reactive hyperplasia,19cases were positive while1case was negative, the positive rate was95%. The expression of Caspase-3in lymph nodes with reactive hyperplasia is higher than that in cases of B-NHL, the difference was statistically significant (χ2=6.750, P<0.05). There were no significant differences between the expression of Caspase-3in B-NHL and their clinopathological parameters of lymphoma (P>0.05).5. The PCNA protein was expressed in nucleus with a brownish yellow or brown granular appearance. In the50cases of B-NHL, the positive rate of PCNA positive was (59.94±20.02)%; In the20cases of lymph nodes with reactive hyperplasia, the positive rate of PCNA was (9.7±8.7)%. The expression of PCNA in B-NHL is higher than that in lymph nodes with reactive hyperplasia, the difference was statistically significant (t=10.776, P<0.05).The expression of PCNA shows the correlation with clinical stage in B-NHL (t=-2.223, P=0.031), there were no significant differences between the expression of PCNA and other pathological parameters of lymphoma (P>0.05).6. In B-NHL, the expression of XIAP and Survivin showed positive correlation (r=0.616, P<0.01); There was no obvious correlation between the expression of XIAP and Bcl-2(r=0.162, P>0.05); The expression of XIAP and Caspase-3showed negatively correlated (r=-0.289, P<0.05); The expression of XIAP and PCNA showed positive correlation (r=0.328, P<0.05); The expression of Survivin and Caspase-3showed negatively correlated(r=-0.156, P<0.05); The expression of Bcl-2and Caspase-3showed negatively correlated(r=-0.463, P<0.05).Conclusions:1.The expression of XIAP, Survivin and Bcl-2in B-NHL was significantly higher than lymph nodes with reactive hyperplasia, it suggests that XIAP, Survivin and Bcl-2take part in the pathogenesis of B-NHL lymphoma, the possible mechanism is the inhibition of apoptosis in different steps involed in the regulation of apoptosis.2. The expression of Caspase-3was significantly lower than reactive hyperplasia of lymph nodes, suggesting that the lower expression of Caspase-3may be involved in pathogenesis of B-NHL lymphoma;3. The expression of PCNA in B-NHL was significantly higher than lymph nodes with reactive hyperplasia, suggesting that over-proliferation of PCNA also take part in the pathogenesis is also involved in occurrence of B-NHL lymphoma;4. The expression of XIAP and Survivin showed positive correlation, suggesting that they may be synergistically involved in the pathogenesis of B-NHL lymphoma;5.There was no obvious correlation between the expression of XIAP and Bcl-2, suggesting that they may participate the pathogenesis through different pathways;6.The expression of XIAP、Survivi、Bcl-2and Caspase-3showed negatively correlated, elucidating that the mechanism of XIAP、Survivin and Bcl-2inhibition apoptosis associated with Caspase-3;7. The expression of XIAP and PCNA showed positive correlation, suggesting in the pathogenesis of B-NHL lymphoma, XIAP not only can inhibit apoptosis, but also can promote cell proliferation.