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

Jane N. Winter, Shuli Li, Vikas Aurora, Daina Variakojis, Beverly Nelson, Maryla Krajewska, Lijun Zhang, Thomas M. Habermann, Richard I. Fisher, William R. Macon, Mukesh Chhanabhai, Raymond E. Felgar, Eric D. Hsi, L. Jeffrey Medeiros, James K. Weick, Edie A. Weller, Ari Melnick, John C. Reed, Sandra J. Horning, Randy D. Gascoyne

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Purpose: 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. Experimental Design: 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 failurefree 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.

Original languageEnglish (US)
Pages (from-to)2435-2442
Number of pages8
JournalClinical Cancer Research
Volume16
Issue number8
DOIs
StatePublished - Apr 15 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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