title: Prognostic significance of survivin expression in diffuse large B-cell lymphomas.
abstract: Survivin is an inhibitor of apoptosis overexpressed in various human cancers but undetectable in normal differentiated tissues. A potential expression and prognostic significance of survivin was studied in 222 patients with diffuse large B-cell lymphomas (centroblastic, 96%; immunoblastic, 4%). All patients were enrolled between 1987 and 1993 (median follow-up, 7 years) in the LNH87 protocol of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA) and treated either with the reference ACVBP arm (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone)[AU3A] (n = 79) or other experimental anthracycline-containing regimens (n = 143). The characteristics of these patients were median age of 56 years; serum lactate dehydrogenase (LDH) greater than 1N, 60%; stage III-IV, 55%; performance status, according to the Eastern Cooperative Oncology Group (ECOG) scale, more than 1, 23%; extranodal sites more than 1, 29%; mass more than 10 cm, 44%; bone marrow involvement, 15%. Of the 222 patients studied, 134 (60%) revealed survivin expression in virtually all tumor cells by immunohistochemistry. The overall 5-year survival rate was significantly lower in patients with survivin expression than in those without (40% vs 54%, P =.02). Multivariate analysis incorporating prognostic factors from the International Prognostic Index (IPI) identified survivin expression as an independent predictive parameter on survival (P =.03, relative risk [RR] = 1.6) in addition to LDH (P =.02, RR = 1.6), stage (P =.03, RR = 1.7), and ECOG scale (P =.05, RR = 1.6). A second analysis incorporating IPI as a unique parameter demonstrated that survivin expression (P =.02, RR = 1.6) remained a prognostic factor for survival independently of IPI (P =.001, RR = 1.5). Survivin expression may be considered a new unfavorable prognostic factor of diffuse large B-cell lymphoma. (Blood. 2000;96:1921-1925)
authors.affiliation: Department of Pathology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: C
authors.initials: C
authors.lastname: Adida
authors.forename: C
authors.initials: C
authors.lastname: Haioun
authors.forename: P
authors.initials: P
authors.lastname: Gaulard
authors.forename: E
authors.initials: E
authors.lastname: Lepage
authors.forename: P
authors.initials: P
authors.lastname: Morel
authors.forename: J
authors.initials: J
authors.lastname: Briere
authors.forename: H
authors.initials: H
authors.lastname: Dombret
authors.forename: F
authors.initials: F
authors.lastname: Reyes
authors.forename: J
authors.initials: J
authors.lastname: Diebold
authors.forename: C
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: G
authors.initials: G
authors.lastname: Salles
authors.forename: D C
authors.initials: DC
authors.lastname: Altieri
authors.forename: T J
authors.initials: TJ
authors.lastname: Molina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins; D011379:Prognosis; D014176:Protein Biosynthesis; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin