title: The importance of Myd88 L265P mutation, clinical and immunohistochemical prognostic factors for the survival of patients with diffuse large B-cell non-Hodgkin lymphoma treated by immunochemotherapy in southeast Serbia.
abstract: OBJECTIVE
  Immunochemotherapy used in the treatment of non-Hodgkin diffuse large B-cell lymphoma (DLBCL) modifies the course of disease and has a positive effect on overall survival (OS). The purpose of this study was to verify the existence of the important Myd 88 mutation and other immunohistochemical factors on disease prognosis in patients with DLBCL in southeast Serbia.
  
  
  METHODS
  Immunohistochemical expression of CD10, Bcl- 2, Bcl-6, Ki-67 and MUM 1 was performed using paraffin blocks of DLBCL. Molecular-genetic study of MyD88 L265P gene polymorphism was done by isolation of genomic DNA from paraffin embedded tissue by means of polymerase chain reaction (PCR).
  
  
  RESULTS
  Immunochemotherapy (rituximab+CHOP/R-CHOP) significantly improved the overall survival (OS) of patients with DLBCL compared with patients treated with CHOP alone (p<0.0001). OS in the R-CHOP group was longest in patients with International Prognostic Index (IPI) 2 score (p=0.012) and IPI 4 score (p=0.024). Patients with Bcl-2 +, and MUM 1+ benefited from R-CHOP and their expression had no effect on OS. Analysis of restriction fragment length on the genomic DNA showed a homozygous normal TT genotype.
  
  
  CONCLUSIONS
  Addition of rituximab to CHOP standard protocol improved the OS rate in patients with DLBCL and altered the character and significance of previously recognized prognostic factors. IPI score in the immunochemotherapy era could not reveal possible predictive factors of poor prognosis which would help identify a high-risk subgroup of newly diagnosed DLBCL. In the patient population from Southeast Serbia pathological signaling pathway achieved by Myd 88 L265 mutation was not responsible for the development of DLBCL.
authors.affiliation: Military Hospital Nis, Department of Internal Medicine, Nis, Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Tadic
authors.forename: Goran
authors.initials: G
authors.lastname: Marjanovic
authors.forename: Lana
authors.initials: L
authors.lastname: Macukanovic-Golubovic
authors.forename: Miljan
authors.initials: M
authors.lastname: Krstic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Jevtovic-Stoimenov
authors.forename: Milos
authors.initials: M
authors.lastname: Kostov
authors.forename: Zaklina
authors.initials: Z
authors.lastname: Smelcerovic
authors.forename: Mariola
authors.initials: M
authors.lastname: Stojanovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000235:genetics*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004252:DNA Mutational Analysis; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D050835:Interferon Regulatory Factors / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D015260:Neprilysin / Q000032:analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000032:analysis; D012307:Risk Factors; D000069283:Rituximab / Q000008:administration & dosage; D055771:Serbia; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult; D000099218:Interferon Regulatory Factor-4
chemical_list: D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D004317:Doxorubicin; D050835:Interferon Regulatory Factors; D019394:Ki-67 Antigen; D053594:Myeloid Differentiation Factor 88; D015260:Neprilysin; D011239:Prednisolone; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D014750:Vincristine; D000099218:Interferon Regulatory Factor-4; C000595707:BCL2 protein, human; C084103:BCL6 protein, human; C507779:MYD88 protein, human