Japanese Journal of Clinical Oncology Advance Access published online on April 24, 2009
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyp037
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© The Author (2009). Published by Oxford University Press. All rights reserved
NF-
B Activation Through the Alternative Pathway Correlates with Chemoresistance and Poor Survival in Extranodal NK/T-cell Lymphoma, Nasal Type
1 Department of Pathology, Shanghai Medical College, Fudan University
2 Department of Medical Oncology, Cancer Hospital, Shanghai Medical College, Fudan University
3 Department of Radiation Oncology, Cancer Hospital, Shanghai Medical College, Fudan University, Shanghai, China
For reprints and all correspondence: Ye Guo, Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, China. E-mail: medoncol{at}gmail.com
Received January 11, 2009; accepted March 18, 2009
Objective: Nuclear factor-
B (NF-B) activation has been identified in a variety of solid tumors and lymphoid malignancies. The aim of our study was to determine the expression status and clinical significance of NF-B in extranodal natural killer (NK)/T-cell lymphoma, nasal type.
Methods: Tumor specimens from 23 patients with previously untreated NK/T-cell lymphoma initially treated with cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP) or CHOP-based chemotherapy were examined by immunohistochemistry for three NF-B subunits (p65, p50 and p52), which are involved in either the canonical or alternative pathway.
Results: None of the cases could be detected with p65 or p50 nuclear staining. On the other hand, 15 (65.2%) cases had p52 nuclear staining, suggesting NF-B activation through the alternative pathway. All major clinical characteristics were balanced between NF-B p52-positive and -negative patients. The objective response rate achieved in NF-B-positive patients was significantly lower than that in negative patients (33.3% vs. 87.5%, P = 0.027). At a median follow-up of 25 months, 8 (53.3%) of 15 NF-B-positive patients had died compared with none of 8 NF-B-negative patients (P = 0.041). In a multivariate analysis, NF-B status and stage were identified to be independent prognostic factors.
Conclusions: Our results suggest that NF-B activation through the alternative pathway is frequently observed in NK/T-cell lymphoma and associated with chemoresistance and poor survival.
Key Words: NK/T-cell lymphoma • NF-B • p52 • chemotherapy
These authors contributed equally to this work.