IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2010;3(1):55-68

Original Article
Tissue‐microarray based immunohistochemical analysis of survival pathways in
nodular sclerosing classical Hodgkin lymphoma as compared with Non‐Hodgkin’s
lymphoma

Jitakshi De, Robert E. Brown

Department of Pathology and Laboratory Medicine at University of Texas Medical School at Houston

Received January 18, 2010, accepted January 25, 2010, available online January 30, 2010

Abstract: Neoplastic cells rely on key oncogenic pathways for their gain of proliferative and/or loss of apoptotic potential. Therapy
targeted at specific points in these pathways has the potential to eliminate cancer cells by inducing differentiation or apoptosis.
Concurrent immunophenotypic evaluation of survival pathways in nodular sclerosing classical Hodgkin lymphoma (cHL‐NS) tissues
has not previously been undertaken. We took the tissue microarray (TMA)‐based approach to retrospectively evaluate the activation
state of key oncogenic pathways by immunohistochemistry (IHC) in a series of 6 cases of cHL‐NS (with predominantly syncitial
areas). For comparison, 2 cases of diffuse large B‐cell lymphoma (DLBCL), and 1 case of follicular hyperplasia (FH) were included in
the study. Infiltration of T regulatory cells (Tregs) in the tumor microenvironment was assessed by expression of the Foxp3 transcription
factor. Differential upregulation of the mitogen‐activated protein kinase (MAPK)‐extracellular signal related kinase (ERK), signal
transducers and activators of transcription (STAT)3, and protein kinase c – alpha (PKC‐α) pathways was seen among the cHL cases,
whereas nuclear factor – kappa B (NF‐κB) and phosphoinositide 3 kinase (PI3 K)‐AKT‐mammalian target of rapamycin (mTOR)
pathways were equally activated in the neoplastic Reed‐Sternberg cells of the 6 cHL‐NS cases. Marked difference in the
morphoproteomic profile was seen amongst the two cases of DLBCL. The amount of Foxp3+ T regulatory cells (Tregs) in the tumor
microenvironment was highly variable ranging from 6/hpf to 120/hpf in cHL‐NS, and 1/hpf to 82/hpf in DLBCL. In this pilot study,
concurrent evaluation of oncogenic pathways in cHL‐NS and DLBCL offers powerful insights in the putative therapeutic targets for an
individualized approach to diagnosis and therapy.(IJCEM1001007).

Key words: Classical Hodgkin lymphoma, diffuse large B‐cell lymphoma, survival pathways, tissue microarray, morphoproteomics

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Address all correspondence to:
Robert E. Brown, MD
Harvey S Rosenberg Endowed Chair
Professor and Vice Chair, Anatomic Pathology
University of Texas- Houston Medical School
Tel. # 1-713-500-5332. Fax #: 1-713-500-0695
E-mail:
Robert.Brown@uth.tmc.edu