Analysis Of The Expressions Of PTEN And VEGF And Microvessel Density In Non-hodgkin’s Lymphoma

Non-Hodgkin’s lymphoma(NHL) is a common lymphatic malignancy with complicated clinical classifications, whose diagnosis,treatment and prognosis vary from its pathological type. The mechanism, diagnosis and treatment of it has become more and more popular. The pathogenesis of non-Hodgkin’s lymphoma remains unclear. Tumor angiogenesis is involved its occurrence, development, infiltration and invasion, which has been found in most solid tumor researches.The process of angiogenesis involves a variety of cytokines, such as hypoxia-inducible factor(HIF), matrix metalloproteinase family(MMPs), and tensin homolog deleted on chromosome 10 phosphatase gene(PTEN), vascular endothelial growth factor(VEGF). Microvessel density(MVD) is regarded as an important indicator of tumor angiogenesis, which can determine tumor growth, proliferation, invasion and prognosis and reflect the effect of anti-tumor therapy. In this study, immunohistochemistry was used to detect the expression of VEGF and PTEN in tissues from Non-Hodgkin’s lymphomas and reactive lymphoid hyperplasias(RHL), measure microvessel density in different tissues.We analyzed the relationship between VEGF and microvessel density and PTEN and microvessel density,in order to achieve the following goals: first, to find a new antigen of clinical significance in non-Hodgkin lymphoma to evaluate the degree of malignancy and help prognosis assessment; second, to find a new target for gene therapy and anti-angiogenic therapy.ObjectiveTo measure the expression of PTEN, VEGF and MVD in non-Hodgkin’s lymphoma, analyze the relationship between each one and the clinical and pathological features of non-Hodgkin’s lymphoma, observe the correlation between PTEN expression and MVD, VEGF expression and MVD, PTEN expression and VEGF expression in the experiment, then test the probable roles of VEGF and PTEN in angiogenesis and the process of evolution of non-Hodgkin’s lymphoma to identify new clinical indicators to evaluate the degree of malignancy and help assess prognosis and provide a new horizon to targeted gene therapy and anti-angiogenesis therapy.MethodsImmunohistochemistry was used to detect VEGF expression, PTEN expression, MVD from 54 cases of non-Hodgkin’s lymphoma and 40 cases of reactive lymphoid hyperplasias. VEGF expression, PTEN expression and MVD, combined with its clinical and pathological features, were analyzed to determine the clinical significance of each indicator. We also analyzed the correlations between every two indicators out of the three indicators to understand their impacts on the development of non-Hodgkin’s lymphoma, on the other hand, to explore the factors in the process of tumor angiogenesis.Result1、Expression of VEGF in non-Hodgkin’s lymphoma and its relationship to the clinical characteristicsThe high expression level of VEGF(42.5%) in the tissue of reactive lymphoid hyperplasia was lower than that in non-Hodgkin’s lymphoma(75.9%).The difference was statistically significant(P <0.05).VEGF expression in non-Hodgkin’s lymphoma showed no relationship to the patient’s sex, age, B symptoms and clinical stage(all P> 0.05), but had relationship to its pathological type(P <0.05). VEGF expression in aggressive lymphoma was higher than that in indolent lymphoma, the difference was statistically significant.2、Expression of PTEN in non-Hodgkin’s lymphoma and its relationship to the clinical characteristicsThe high expression level of PTEN(70%) in the tissue of reactive lymphoid hyperplasia was higher than that in non-Hodgkin’s lymphoma(29.8%).The difference was statistically significant(P <0.05).PTEN expression in non-Hodgkin’s lymphoma showed no relationship to the patient’s sex, age and B symptoms(all P> 0.05), but had relationship to its pathological type and clinical stage(P <0.05). PTEN expression in aggressive lymphoma was lower than that in indolent lymphoma.The expression in lymphoma with late clinical stages(Ⅲ、Ⅳ)was lower than that in lymphoma with early clinical stages(Ⅰ、Ⅱ).The differences were both statistically significant.3、MVD in non-Hodgkin’s lymphoma and its relationship to the clinical characteristicsThe MVD in the tissue of reactive lymphoid hyperplasia(11.09±2.18)was lower than that in non-Hodgkin’s lymphoma(24.13±4.17).The difference was statistically significant(P <0.05).MVD in non-Hodgkin’s lymphoma showed no relationship to the patient’s sex, age and B symptoms(all P> 0.05), but had relationship to its pathological type and clinical stage(P <0.05). MVD in aggressive lymphoma was higher than that in indolent lymphoma.The expression in lymphoma with late clinical stages(Ⅲ、Ⅳ)was higher than that in lymphoma with early clinical stages(Ⅰ、Ⅱ).The differences were both statistically significant.4 、 Analysis of correlations between VEGF expression and PTEN expression, VEGF expression and MVD, PTEN expression and MVDSpearman’s test showed: expression of VEGF was negatively correlated with that of PTEN(P <0.05); PTEN expression was negatively correlated with MVD(P <0.05); VEGF expression was positively correlated with MVD(P <0.05).Conclusion1、VEGF and PTEN play different roles in the tumor angiogenesis; VEGF can promote angiogenesis, PTEN acted as an inhibitory role.The two factors plays contrary roles in angiogenesis.2、PTEN is a tumor suppressor, whose deletion or mutation resulted in the lack of the PTEN protein associated with the invasion, development of non-Hodgkin’s lymphoma, suggesting that it may be a new indicator of non-Hodgkin’s lymphoma with effective application.3、Based on the association with the development and metastasis of non-Hodgkin’s lymphoma, anti-angiogenic therapy targeting PTEN at protein level or at the gene level may improve the treatment of non-Hodgkin’s lymphoma.