title: c-FLIP does not correlate with response to immunochemotherapy treatment and outcome of patients with nodal diffuse large B-cell lymphoma.
abstract: Cellular FLICE-inhibitory protein (c-FLIP) is a critical anti-apoptotic regulator that inhibits apoptosis-inducing ligand, (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. The present study was designed to investigate the clinical and prognostic significance of c-FLIP expression in patients with nodal diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy.
  
  
  METHODS
  We have analyzed lymph node biopsy specimens, obtained from 60 patients with newly diagnosed nodal DLBCL treated with immunochemotherapy (R-CHOP or R-EPOCH). The expression of c-FLIP was analyzed using the standard imunohistochemical method on formalin-fixed and routinely processed paraffin-embedded lymph node specimens and evaluated semi quantitavely as a percentage of tumor cells.
  
  
  RESULTS
  c-FLIP immunoexpression (>50% positive tumor cells) has been found in 28 (46.7%) patients, and observed as cytoplasmic staining. There was not significant difference in c-FLIP immunoexpression between GCB and non-GCB subtype of DLBCL (P=0.639). Besides, c-FLIP immunoexpression had no significant association with IPI, "bulky" disease, extranodal localization, haemoglobin, Ki-67 immunoexpression or other clinico-pathological parameters. c-FLIP positivity has no significant influence on therapy response and survival in patients with DLBCL (P=0.562 and P=0.093, respectively). Patients with c-FLIP overexpression did not relapse more often that patients without expression of this apoptotic protein (P=0.365).
  
  
  CONCLUSIONS
  Our results suggest that c-FLIP immunoexpression can not be used as a prognostic factor in patients with nodal DLBCL treated with immunochemotherapy.
authors.affiliation: Clinical Hospital Center "Bezanijska kosa", Belgrade, Serbia. omarkovic@bkosa.edu.rs
authors.forename: Olivera
authors.initials: O
authors.lastname: Markovic
authors.forename: Dragomir
authors.initials: D
authors.lastname: Marisavljevic
authors.forename: Vesna
authors.initials: V
authors.lastname: Cemerikic-Martinovic
authors.forename: Branka
authors.initials: B
authors.lastname: Filipovic
authors.forename: Slavica
authors.initials: S
authors.lastname: Radovanović
authors.forename: Marija
authors.initials: M
authors.lastname: Zdravković
authors.forename: Dejana
authors.initials: D
authors.lastname: Stanisavljevic
authors.forename: Biljana
authors.initials: B
authors.lastname: Mihaljevic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000276:immunology / Q000378:metabolism*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D021701:Sentinel Lymph Node Biopsy; D013534:Survival; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone