[Expression of natural killer cell development-associated transcription factors in nasal NK/T-cell lymphomas occurring in Chinese population].
OBJECTIVE
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 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.
Department of Pathology, Peking University First Hospital, Beijing 100034, China.
Shuang
S
Zhang
Lin
L
Nong
Ying
Y
Zhang
Ying
Y
Wang
Ting
T
Li
D000293:Adolescent; D000328:Adult; D000368:Aged; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell; D016411:Lymphoma, T-Cell, Peripheral / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009669:Nose Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015996:Survival Rate; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D055815:Young Adult; D000098815:T-bet Transcription Factor
D004268:DNA-Binding Proteins; C111931:ELF4 protein, human; C491199:EOMES protein, human; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors