Table of Contents
Lymphoma
Volume 2012 (2012), Article ID 341629, 12 pages
http://dx.doi.org/10.1155/2012/341629
Research Article

Analysis of NF- B Pathway Proteins in Pediatric Hodgkin Lymphoma: Correlations with EBV Status and Clinical Outcome—A Children's Oncology Group Study

1Texas Children's Hospital and Dan L. Duncan Cancer Center, Baylor College of Medicine, Suite 750, 1102 Bates Street, Houston, TX 77030, USA
2Department of Pathology, Texas Children's Hospital and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
3Department of Pathology, SUNY Upstate Medical University, 750 E. Adam Street, Syracuse, NY 13210, USA
4Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
5Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA

Received 3 August 2012; Accepted 6 November 2012

Academic Editor: Juan F. Garci­a

Copyright © 2012 Terzah M. Horton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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- , IKK- , IKK- , 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.