title: Expression of p21 protein predicts clinical outcome in DLBCL patients older than 60 years treated with R-CHOP but not CHOP: a prospective ECOG and Southwest Oncology Group correlative study on E4494.
abstract: OBJECTIVE
  To prospectively investigate the prognostic significance of p21 and p53 expression in diffuse large B-cell lymphoma in the context of the U.S. Intergroup trial comparing conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to rituximab-CHOP (R-CHOP) induction, with or without maintenance rituximab.
  
  
  METHODS
  Immunohistochemical staining of 197 paraffin-embedded biopsy specimens was scored by an independent panel of experts.
  
  
  RESULTS
  The cyclin-dependent kinase inhibitor, p21, was expressed in 55% of cases examined. In a multivariable analysis adjusting for International Prognostic Index score and BCL2 status, p21 expression was a significant, independent, favorable predictive factor for failure-free survival (relative risk, 0.3; P = 0.001) and overall survival (relative risk, 0.3; P = 0.003) for patients treated with R-CHOP. Expression of p21 was not predictive of outcome for CHOP-treated patients. Only p21-positive cases benefited from the addition of rituximab to CHOP. Among p21-positive patients, treatment with R-CHOP was associated with a higher failure-free survival rate at 5 years compared with CHOP (61% versus 24%; P = 0.01). In contrast, no significant differences were detected in failure-free survival according to treatment arm for p21-negative patients. Expression of p53, alone or in combination with p21, did not predict for outcome in univariable or multivariable analyses.
  
  
  CONCLUSIONS
  In this study, p21 protein expression emerged as an important independent predictor of a favorable clinical outcome when rituximab was added to CHOP therapy. These data suggest that rituximab-related effects on lymphoma survival pathways may be functionally linked to p21 activity.
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. j-winter@northwestern.edu
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.forename: Vikas
authors.initials: V
authors.lastname: Aurora
authors.forename: Daina
authors.initials: D
authors.lastname: Variakojis
authors.forename: Beverly
authors.initials: B
authors.lastname: Nelson
authors.forename: Maryla
authors.initials: M
authors.lastname: Krajewska
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Felgar
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: James K
authors.initials: JK
authors.lastname: Weick
authors.forename: Edie A
authors.initials: EA
authors.lastname: Weller
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone