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- Title
Analysis of NF-?B Pathway Proteins in Pediatric Hodgkin Lymphoma: Correlations with EBV Status and Clinical Outcome--A Children's Oncology Group Study.
- Authors
Horton, Terzah M.; Sheehan, Andrea M.; López-Terrada, Dolores; Hutchison, Robert E.; Narendra, Sonia; Wu, Meng-Fen; Hao Liu
- Abstract
Constitutively active nuclear factor-?B (NF-?B) is integral to the survival of Hodgkin/Reed-Sternberg cells (H/RS) in Hodgkin lymphoma (HL). To investigate NF-?B pathway proteins in pediatric HL, we utilized a tissue microarray compiled from 102 children enrolled in the Children's Oncology Group intermediate-risk clinical trial AHOD0031 (56 male, 78 Caucasian, median age 15 years (range 1-20 years), 85 nodular sclerosing subtype, 23 Epstein-Barr virus (EBV) positive, and 24 refractory/relapsed disease). We examined the intensity, localization, and pathway correlations of NF-?B pathway proteins (Rel-A/p65, Rel-B, c-Rel, NF-?B1, NF-?B2, I?B-a, IKK-a, IKK-ß, IKK-?/NEMO, NIK, and A20), as well as their associations with EBV status and clinical outcome. NF-?B pathway proteins were overexpressed in pediatric HL patients compared to controls. Patients with EBV- tumors, or with rapid early therapy response, had tightly coordinated regulation of NF-?B pathway proteins, whereas patients with EBV+ tumors, or slow early therapy response, had little coordinated NF-?B pathway regulation. High NIK expression was associated with a slow response to therapy and decreased EFS. Elevated Rel-B, NIK, and the NF-?B inhibitor A20 were associated with decreased EFS in multivariate analysis. These studies suggest a pivotal role for the NF-?B pathway in therapy response and patient survival in Hodgkin lymphoma.
- Subjects
HODGKIN'S disease in children; HODGKIN'S disease; NF-kappa B; HEALTH outcome assessment; CLINICAL trials; AGE factors in disease; DISEASE risk factors; THERAPEUTICS
- Publication
Lymphoma (2090309X), 2012, p1
- ISSN
2090-309X
- Publication type
Article
- DOI
10.1155/2012/341629