| The progression of technique brings us deeper insight of the nature about diseases. The classifications of tumors have developed from simply morphological classification to the more sceincific ones which based on the clinical, morphological, immunophenotypic, biological and molecular genetic features. According to this, the classification of heamatopoietic and lymphoid neoplasms of WHO identified formally the criteria of extranodal NK/T-cell lymphoma, nasal-type in 2001. Its distinct clinical, pathological, and immunophenotypic features have now been well recognized. For example, N-NK/T-L was characteristic of coagulative necrosis, inflammatory background and angiodestructive growth pattern. Besides, a panel of antibodies including CD43/CD45RO, CD3ε, CD56 and TIA-1, and in-situ hybridization detecting EBV infection were used for regular diagnosis. However, little is known about it's prognostic factors, specific phenotypes, etiology and genesis, and so far no specific genetic aberrations have been identified. So it is urgent to investigate specific genetic alterations and markers for defineing specific disease entities and accurate diagnosis. Recently, our study group found T-bet gene amplification in N-NK/T-L, after the previous study of p53 and c-kit mutation, through the analysis of RLGS (restriction landmark genomic scanning) and VGS (virtual genome scan) which applied to genomic DNA that extracted from N-NK/T-L cells and peripheral blood leukocytes of the same patient. The amplification of T-bet gene were confirmed by Southern and dot blotting which were applied to 3 cases of N-NK/T-L cells and 1 case of peripheral blood leukocytes, and in-situ hybridization in tissue sections of 20 N-NK/T-L, 17 B cell lymphoma (BCL), 3 spleens and 5 chronic nasopharyngitis.Several fundamental researchs show that EOMES gene which, as a paralogue of T-bet gene, belongs to T-box family either is a partner of T-bet gene or has the similar function in lymphoid development, differentiation, mature and function. Moreover, The ETS family gene ETS-1 and MEF both involve in the lymphoid development and the production of IFN-γ, perforin and granzyme B. It is a common sense that multigene involve in tumorigenesis. So based on the found of T-bet, we explore the expression of EOMES, ETS-1 and ETS-1 genes to investigate their function in N-NK/T-L by in situ hybridization. The results were as follow:1. The expression of EOMES was detected in all 25 cases of N-NK/T-L, in which 13 (52%) cases were high, 8 (32%) were intermediate. In the control group, 10 of 11 cases of BCL were positive (6 cases intermediate and 4 cases low), 5 of 6 cases of TCL showed positive staining (1 case intermediate and 4 cases low). The statistic calculation showed that the difference of EOMES expression between N-NK/T-L and BCL/TCL was significant (P<0.05). 2 expressions of EOMES were detected in the three normal spleen tissues group and the five chronic inflammatory nasal mucosa group respectively.2. The expression of MEF was detected in 24 cases of N-NK/T-L, in which 6 (24%) cases were high, 11 (44%) were intermediate. In the control group, 9 cases of BCL presented positive staining (7 cases intermediate and 2 cases low), 3 cases of TCL were positive staining (1 case intermediate and 2 cases low). The statistic calculation suggested that the difference of MEF expression between N-NK/T-L and TCL was significant (P<0.05) (Table 3). 1 expression of MEF was detected in the three normal spleen tissues group and the five tissues of chronic inflammatory nasal mucosa group respectively.3. The expression of ETS-1 was detectable in all cases of N-NK/T-L and the control group.4. By analyzing all 50 cases of tumours and normal tissues, we found the correlationship exist between EOMES and MEF (P<0.0001). And the analyses based on the 40 cases which were used in the last experiment about T-bet gene revealed the correlationships existing between T-BET and EOMES (P=0.0295), T-BET and MEF (P=0.0008).In conclusion, these results indicate the expression of EOMES and MEF gene may function in the development of N-NK/T-L and the tumor necrosis and the general expression of ETS-1 gene may be a fundamental common part of the program of lymphoid development and function. |
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