Transcription factors engaged in development of NK cells are commonly expressed in nasal NK/T-cell lymphomas

Abstract

Extranodal natural killer/T (NK/T)-cell lymphoma, nasal type, is a prevailing tumor in Asia with distinct clinical, pathologic, and immunophenotypic features. Previous study revealed amplification and overexpression of T-bet in extranodal NK/T-cell lymphoma, nasal type. As a transcription factor, T-bet functionally cooperates with its family member eomesodermin (EOMES) or ETS family members (ETS-1 and MEF) and positively regulates the development and cytotoxic function of natural killer (NK) cells. To evaluate their role in extranodal NK/T-cell lymphoma, nasal type, the expression status and clinical relevance of these genes were analyzed in 40 cases of this tumor by in situ hybridization and immunohistochemistry. Tumor cells in all 40 cases expressed cytotoxic granule proteins, of which 39 contained the Epstein-Barr virus (EBV) genome. Two (8.7%) of 23 cases showed T-cell receptor (TCR) γ gene clonal rearrangement, confirming cytotoxic T lineage of cell derivation. The expression level of T-bet as revealed by in situ hybridization and immunohistochemistry was high in extranodal NK/T-cell lymphoma, nasal type, (82.5% and 100%) and peripheral T-cell lymphomas (94.4% and 72.2%) but not in mature B-cell lymphomas in our control group (0% and 0%). By in situ hybridization, high expression of EOMES (80.0%), ETS-1 (82.5%), and MEF (62.5%) was observed in cases of extranodal NK/T-cell lymphoma, nasal type, but none of the control groups and cases expressed these molecules. Coexpression of T-bet and EOMES, ETS-1, or MEF was found in 30 (75%), 25 (62.5%), and 21 cases (52.5%), respectively. The frequency of coexpression of T-bet and EOMES was significantly higher than that of other genes. Transcription factors engaged in NK-cell development are highly expressed in extranodal NK/T-cell lymphoma, nasal type, suggesting a role in the biologic behavior of this tumor.