摘要目的 探讨自然杀伤(NK)细胞发育相关转录因子T-bet、EOMES、ETS-1和MEF在结外鼻型NK/T细胞淋巴瘤中的表达及意义.方法 运用原位杂交检测录因子T-bet、EOMES、ETS-1和MEF,应用免疫组织化学(EnVision法)检测T-bet因子在40例结外鼻型NK/T细胞淋巴瘤中表达情况,分析与患者预后的相关性,并与对照组外周T细胞淋巴瘤(PTCL)18例、B细胞淋巴瘤(BCL)10例以及正常脾、胸腺组织各5例和慢性炎性鼻黏膜组织10例进行对比.结果 在结外鼻型NK/T细胞淋巴瘤及PTCL中,T-bet mRNA(82.5%,33/40及17/18)和蛋白(100%,40/40及13/18)呈高表达,而在BCL中不表达.EOMES、ETS-1和MEF在结外鼻型NK/T细胞淋巴瘤呈高表达,分别为80.0%(32/40)、82.5%(33/40)和62.5%(25/40),而对照组均阴性.EOMES和T-bet在40例结外鼻型NK/T细胞淋巴瘤中75%(30/40)共表达,具统计学意义(P<0.01).40例结外鼻型NK/T细胞淋巴瘤患者平均和中位生存期分别为33和10个月,5年生存率10.5%.临床各影响因素中仅治疗方案对预后影响有意义,各转录因子表达对预后影响差异均无统计学意义(P>0.05);9例存活和lO例死亡者中,各转录因子表达差异均无统计学意义(均P>0.05).结论 T-bet表达与淋巴瘤类型有关,主要见于外周NK和T细胞淋巴瘤;NK发育重要功能基因在结外鼻型NK/T细胞淋巴瘤中显著表达,是否为维持肿瘤高度侵袭性生物学行为所必需值得深入探讨.

abstractsObjective 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). Methods 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. Results 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. Conclusions The expression of T-bet correlates with the Iymphoma 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.