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).
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