title: Prognostic significance of BAD and AIF apoptotic pathways in diffuse large B-cell lymphoma.
abstract: BACKGROUND
  To determine whether proapoptotic proteins were associated with clinicopathologic heterogeneity and influenced survival in patients with diffuse large B-cell lymphoma (DLBCL), we evaluated patterns of expression of the BCL-2 family member BAD, PP1alpha (the catalytic subunit of PP1 involved in activation of BAD), and apoptosis-inducing factor (AIF).
  
  
  METHODS
  We retrospectively analyzed 46 patients all treated with standard chemotherapy ([CHOP] cyclophosphamide/doxorubicin/vincristine/prednisone-like); of these, 16 received rituximab. Immunohistochemical analyses were performed from biopsy samples of nodal DLBCL that were performed at initial diagnosis. Normal reactive lymph nodes were used as controls.
  
  
  RESULTS
  BAD expression was found in 38 of 46 DLBCL cases and, though variable, was often strong. PP1alpha and AIF were detected in all tumors tested with a relative strong expression. Lower BAD expression was shown to be significantly associated with advanced clinical stages (Ann Arbor stage III + IV and International Prognostic Index intermediate-high to high; P = .006 and P = .0008, respectively). Moreover, BAD staining was positively correlated with BCL-2 (P = .022) and PP1alpha (P = .013) staining. Finally, high AIF expression proved to be predictive of a longer overall survival in non-rituximab-treated patients.
  
  
  CONCLUSIONS
  Our study shows for the first time in DLBCL that differential BAD expression might play a role in the development of the disease, possibly reflecting its function as a tumor suppressor. Furthermore, our data highlight the interest in targeting BAD phosphatases and AIF-mediated mitochondrial apoptosis for new therapeutic strategies.
authors.affiliation: EA3842, Université de Limoges, France. danielle.troutaud@unilim.fr
authors.forename: Danielle
authors.initials: D
authors.lastname: Troutaud
authors.forename: Barbara
authors.initials: B
authors.lastname: Petit
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bellanger
authors.forename: Benoît
authors.initials: B
authors.lastname: Marin
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Gourin-Chaury
authors.forename: Daniel
authors.initials: D
authors.lastname: Petit
authors.forename: Agnès
authors.initials: A
authors.lastname: Olivrie
authors.forename: Jean
authors.initials: J
authors.lastname: Feuillard
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Jauberteau
authors.forename: Dominique
authors.initials: D
authors.lastname: Bordessoule
mesh_terms: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D013267:Stilbenes; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D051033:Apoptosis Inducing Factor; D013267:Stilbenes; C006711:benzoylamido-4'-aminostilbene-2,2'-disulfonate; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone