NF-kappaB activation through the alternative pathway correlates with chemoresistance and poor survival in extranodal NK/T-cell lymphoma, nasal type.
OBJECTIVE
Nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-kappaB 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-kappaB activation through the alternative pathway. All major clinical characteristics were balanced between NF-kappaB p52-positive and -negative patients. The objective response rate achieved in NF-kappaB-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-kappaB-positive patients had died compared with none of 8 NF-kappaB-negative patients (P = 0.041). In a multivariate analysis, NF-kappaB status and stage were identified to be independent prognostic factors.


CONCLUSIONS
Our results suggest that NF-kappaB activation through the alternative pathway is frequently observed in NK/T-cell lymphoma and associated with chemoresistance and poor survival.
Liu
Xueguang
X
Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai Medical College, Fudan University, Shanghai, China.
Wang
Biyun
B
Ma
Xuejun
X
Guo
Ye
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D054391:Lymphoma, Extranodal NK-T-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D009669:Nose Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D011239:Prednisolone / Q000627:therapeutic use; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
D016328:NF-kappa B; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone