TET2和DNMT3A在外周T细胞淋巴瘤中的表达及其意义

发布时间：2018-06-06 05:02

本文选题：淋巴瘤 + 外周T细胞淋巴瘤　；参考：《青岛大学》2017年硕士论文

【摘要】：目的探讨TET2(ten-eleven-trantranslocation 2)和DNMT3A(DNA Methyltransferase 3A)在外周T细胞淋巴瘤(peripheral T-cell lymphoma,PTCL)各亚型中的表达情况及意义,及其与外周T细胞淋巴瘤免疫分型及临床病理特征的关系及意义。方法1.根据已标记的一系列免疫组织化学标记:CD3、CD4、CD10、BCL-6、CXCL-13、CD30、EMA、ALK(缺少标记的补做),可将PTCL患者分为血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T cell lymphoma,AITL)、外周T细胞淋巴瘤,非特指(peripheral T-cell lymphomas,not otherwides,PTCL-NOS)、间变性淋巴瘤激酶阳性的间变性大细胞淋巴瘤(anaplastic lymphoma kinase positive anaplastic large cell lymphoma,ALK+ALCL)和间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤(anaplastic lymphoma kinase negative anaplastic large cell lymphoma,ALK-ALCL)四种类型。2.应用免疫组织化学方法检测89例PTCL患者组织中TET2和DNMT3A的表达情况,分析二者表达的相关关系及与PTCL各亚型及临床病理特征的关系。结果1.89例PTCL病例中,AITL36例,占40.44%,PTCL-NOS26例,占29.21%,ALK-ALCL18例,占20.22%,ALK+ALCL9例,占10.11%。2.TET2和DNMT3A在PTCL病例中均表达与细胞质及细胞核。3.TET2和DNMT3A在AITL病例中高表达率均高于PTCL-NOS(P=0.005,P=0.048)、ALCL(P=0.001,P=0.001),差异均有统计学意义。4.在细胞质表达中,TET2细胞质表达的高表达率在AITL病例中均高于PTCL-NOS(P=0.001)和ALCL(P0.001),差异均有统计学意义;DNMT3A细胞质表达的高表达率在AITL病例中均高于PTCL-NOS(P=0.029)、ALCL(P=0.024),差异均有统计学意义。5.在细胞核表达中,DNMT3A细胞核表达的高表达率在AITL中均高于PTCL-NOS(P=0.047)、ALCL(P0.001),差异均有统计学意义。6.在PTCL病例中,TET2表达和DNMT3A表达成正相关关系(r=0.384,P0.001);TET2细胞质表达和DNMT3A细胞质表达成正相关关系(r=0.350,P=0.001);TET2细胞质表达和DNMT3A胞核表达成正相关关系(r=0.365,P0.001)。7.在AITL病例中,TET2表达和DNMT3A表达成正相关关系(r=0.478,P=0.003);TET2细胞质表达和DNMT3A细胞质表达成正相关关系(r=0.336,P=0.045);TET2细胞质表达和DNMT3A细胞核表达成正相关关系(r=0.478,P=0.003)。8.有B症状PTCL患者中TET2细胞核高表达率高于无B症状患者,差异有统计学意义(P=0.003);在III+IV期PTCL患者中,TET2细胞质高表达率高于I+II期PTCL患者,差异虽无统计学意义,但处于临界水平(P=0.061)。9.TET2和DNMT3A的表达与PTCL患者年龄、性别、LDH水平和IPI评分、结外浸润无关。结论TET2和DNMT3A异常可能均参与了PTCL的发病,TET2和DNMT3A失活导致DNA甲基化异常及造血干细胞增殖和分化异常进而可能参与了PTLC的发生发展,为PTCL的治疗提供了新的研究思路和策略。TET2和DNMT3A可以作为明确诊断AITL的分子标志物,为AITL的明确诊断提供了新的策略。
[Abstract]:Objective to investigate the expression and significance of TET2(ten-eleven-trantranslocation _ 2 and DNMT3A(DNA Methyltransferase _ 3A in peripheral T-cell lymphoma of peripheral T cell lymphoma and their relationship with the immunological classification and clinicopathological features of peripheral T cell lymphoma. Method 1. According to a series of labeled immunocytochemical markers: CD10CL-6, CXCL-13, CD30, EMA-ALK, PTCL patients can be divided into angioimmunoblastic T cell lymphoma (PTCL) and peripheral T-cell lymphoma (T-cell lymphoma). There were four types of non-specific T-cell lymphomatosis: PTCL-NOSU, anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK ALCLL) and anaplastic large cell lymphoma (ALK-ALCLL) and anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK-ALCLL). Immunohistochemical method was used to detect the expression of TET2 and DNMT3A in 89 patients with PTCL. The correlation between the expression of TET2 and DNMT3A and the relationship between the expression of TET2 and PTCL subtypes and clinicopathological features were analyzed. Results 1.AITL was found in 36 cases of PTCL, accounting for 40.444.There were 26 cases of PTCL-NOS, accounting for 29.21 cases of ALK-ALCLL, accounting for 20.222 cases of ALK ALCL9. The expression of 10.11%.2.TET2 and DNMT3A in PTCL cases were both higher than those in AITL cases and the high expression rates of cytoplasm and nucleus .3.TET2 and DNMT3A were higher than those in AITL cases. The high expression rate of cytoplasm in AITL was higher than that in PTCL-NOSP 0.001) and ALCLT P0.001. The difference was statistically significant. The high expression rate of cytoplasm of DNMT3A was higher in AITL than that in PTCL-NOSP 0.029 ALCLP0.0244.The difference was statistically significant. The high expression rate of DNMT3A in nuclear expression was higher in AITL than that in PTCL-NOSP 0.047 and ALCLT P0.001, and the difference was statistically significant. There was a positive correlation between the expression of Tet T 2 and the expression of DNMT3A in patients with PTCL. There was a positive correlation between the expression of Tet T 2 and the expression of DNMT3A in the cytoplasm and the cytoplasm of DNMT3A. There was a positive correlation between the expression of T T 2 and the expression of DNMT3A. There was a positive correlation between the expression of Tet T 2 and the expression of DNMT3A in AITL patients. There was a positive correlation between the expression of Tet T 2 and the expression of DNMT3A cytoplasm. There was a positive correlation between the expression of T T 2 and the expression of DNMT3A nucleus. The high expression rate of TET2 nucleus in patients with PTCL with B symptom was higher than that in patients without B symptoms, the difference was statistically significant, and the high expression rate of cytoplasm in patients with PTCL in stage IV of III was higher than that in patients with PTCL in stage I II, although the difference was not statistically significant. However, the expression of PTET2 and DNMT3A at the critical level was not related to age, sex, IPI score and extranodular invasion. Conclusion the abnormality of TET2 and DNMT3A may be involved in the pathogenesis of PTCL. DNA methylation abnormality and abnormal proliferation and differentiation of hematopoietic stem cells may be involved in the pathogenesis of PTCL and the inactivation of TET2 and DNMT3A, which may be involved in the occurrence and development of PTLC. TET2 and DNMT3A can be used as molecular markers for the diagnosis of AITL and a new strategy for the definite diagnosis of AITL.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.1

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