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Japanese Journal of Clinical Oncology

Year: 2009  |  Volume: 39  |  Issue: 7  |  Page No.: 418 - 424

NF-{kappa}B Activation Through the Alternative Pathway Correlates with Chemoresistance and Poor Survival in Extranodal NK/T-cell Lymphoma, Nasal Type

X Liu, B Wang, X Ma and Y. Guo

Abstract

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.

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