Expression of natural killer cell development-associated transcription factors in nasal NK/T-cell lymphomas occurring in Chinese population

Abstract

To evaluate the expression and prognostic significance of T-bet and its cofactors EOMES, ETS-1 and MEF [which are transcription factors and responsible for development of natural killer (NK) cells] in the extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT). The expression status of T-bet, EOMES, ETS-1 and MEF in 40 cases of EN-NK/T-NT occurring in Chinese population was studied by immunohistochemistry and in-situ hybridization (ISH). The clinical relevance was also evaluated. The control cases included 18 cases of peripheral T-cell lymphoma, 10 cases of B-cell lymphoma, 5 cases of normal spleen, 5 cases of normal thymus and 10 cases of nasal mucosal tissues affected by chronic inflammation. The expression levels of T-bet mRNA and protein were high in EN-NK/T-NT (82.5% and 100%, respectively) and in peripheral T cell lymphoma (17/18 and 72.2%, respectively). There was no expression in B-cell lymphoma. The expression of EOMES (80.0% by ISH), ETS-1 (82.5% by ISH) and MEF (62.5% by ISH) was high in EN-NK/T-NT, but not in the control group. The frequency of co-expression of T-bet and EOMES (75%, 30/40) was significantly higher than that of the other genes. Follow-up study showed that the mean and median survival of the 19 cases of EN-NK/ T-NT was 33 months and 10 months, respectively. The five-year survival rate was 10.5%. Statistical analysis showed that only treatment modalities significantly affected the patients' overall survival; and none of the four transcription factors had significant impact on survival. The expression rates of T-bet, EOMES, ETS-1 or MEF had no significant difference between the 9 alive and the 10 dead cases. The expression of T-bet correlates with the lymphoma types. It is mainly expressed in peripheral NK and T-cell lymphomas. The important functional gene engaged in NK cells development is highly expressed in EN-NK/T-NT. They may play a crucial role in pathogenesis and aggressive biologic behavior.