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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: 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 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.

SUBMITTER: Winter JN 

PROVIDER: S-EPMC2865202 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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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.

Winter Jane N JN   Li Shuli S   Aurora Vikas V   Variakojis Daina D   Nelson Beverly B   Krajewska Maryla M   Zhang Lijun L   Habermann Thomas M TM   Fisher Richard I RI   Macon William R WR   Chhanabhai Mukesh M   Felgar Raymond E RE   Hsi Eric D ED   Medeiros L Jeffrey LJ   Weick James K JK   Weller Edie A EA   Melnick Ari A   Reed John C JC   Horning Sandra J SJ   Gascoyne Randy D RD  

Clinical cancer research : an official journal of the American Association for Cancer Research 20100406 8


<h4>Purpose</h4>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.<h4>Experimental design</h4>Immunohistochemical staining of 197 paraffin-embedded biopsy specimens was scored by an independent panel of experts.<  ...[more]

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