Klinički i imunološki faktori prognoze kod bolesnika sa B difuznim krupnoćelijskim nehočkinskim limfomom
Tadić, Ljiljana Lj.
Факултет:Универзитет у Нишу, Медицински факултет
Датум одбране дисертације:12-10-2016
МетаподациПриказ свих података о дисертацији
Patients with diffuse large B cell non Hodgkin lymphoma (DLBCL) have a very heterogeneous clinical course and prognosis. There is a constant need to find new prognostic factors to assess risk in patients. Immunohistochemical biomarkers correlated with clinical and biochemical parameters, as well as prognostic scores may be predictors of risk patients. The main aim of this study was to analyze the survival of patients with diffuse large B- cell non Hodgkin lymphoma according to clinical prognostic factors and expression of proteins involved in the activation of immune response, cell cycle regulation and programmed cell death (Ki-67, Bcl-2, Bcl-6 , CD10, CD5, CD138, MUM1 and the presence of mutations L265P MyD88), by classifying patients according to current prognostic scoring systems comparing the clinical and immunological factors prognosis in patients with DLBCL, make a proposal for a prognostic scoring system that would unite the two groups of parameters. All patients was determined by
clinical stage of the disease. During the study were collected and processed by clinical and laboratory parameters, that are known to have a prognostic value and that it was possible to collect for all patients included in the study. It is about gender, age, Ann Arbor clinical stage of disease, extranodal number of cities affected processes, performance status, presence of "B" symptoms, hemoglobin, platelet count, erythrocyte sedimentation rate, C-reactive protein levels, beta 2 microglobulin, serum albumin and serum LDH. Histopathological material consisted of 68 paraffin blocks. From immunohistochemical parameters were analyzed: CD5, CD10, Ki- 67, Bcl-2, Bcl-6, MUM1 by EnVision procedure. Molecular-genetic study of gene polymorphism MyD88 L265P was used genomic DNA isolated from fixed tissue in paraffin patients with DLBCL. Polymerization chain reaction were amplified by DNA segments within which the SNP is tested gene MyD88 L265P. Statistical analyzes included the use of nonparametric methods and parametric tests. Period of OS (overall survival), was studied using Kaplan-Meier analysis. A statistically significant difference in overall survival (OS) exists in relation to the age (the benefit under the age of 60 years), compared with gender (in favor of women) and the albumin concentration in serum (lower serum albumin levels in patients with DLBCL are associated with shorter OS, as they showed the greatest predictive value). In the prediction of the risk significance showed recategorized performance status (category : ≤2; > 2), recategorized clinical stage of the disease (limited and advanced DLBCL) and R- IPI. The analysis of restriction fragment length is determined homozygous, normal wild type genotype polymorphisms tested. All other clinical, biochemical and immunohistochemical parameters showed no predictive value in patients with DLBCL. in relation to the applied therapeutic protocol there is a strong statistical significance in overall survival in favor of the patients treated at R- CHOP protocol. We standardized PCR-RFLP method for Myd 88 L265P DNA samples isolated from paraffin molds. According to our knowledge there are no data available on the study Myd 88 L265P polymorphism in a population of patients with DLBCL in Serbia. In the population of patients with areas of southeast Serbia pathological signaling pathway which achieves mutation Myd 88 L265, is not responsible for the development DLBCL.Male gender, age over 60, low levels of serum albumin were negative predictor factors in patients with DLBCL. R-IPI score is in the era imunochemotherapy, useful prognostic score in relation to the IPI.Више
Кључне речи:DLBCL, imunohemoterapija, imunohistohemijski parametri, Myd 88 L265P, IPI, R-IPI; DLBCL, imunochemotherapy, immunohistochemical parameters Myd 88 L265P, IPI, R-IPI