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FOXP3在正常人皮肤和表皮肿瘤中的表达及意义

发布时间:2019-06-01 08:56
【摘要】: 研究背景: 以往的研究表明:癌症患者在肿瘤局部和全身的免疫功能都处于耐受或缺陷状态,肿瘤必需在逃逸机体的免疫监控之后才得以发展。调节性T细胞是一类具有免疫调节功能的T淋巴细胞亚群,这类细胞有较强的免疫抑制功能,在肿瘤免疫逃逸中起着十分重要的作用。虽然调节T细胞有多种类型,但是经典的FOXP3+CD4+CD25+调节性T细胞(CD4+CD25+regulatory T cells, CD4+CD25+Treg)是其中最主要的一群细胞,其对自身抗原和外来抗原引发的免疫反应均具有免疫调节作用,是机体维持免疫耐受的重要机制之一。叉头状转录因子P3(forkhead--winged helix transcription factor-3, Foxp3)是叉头状转录因子家族中的一员,对CD4+CD25+调节性T细胞在分化发育、功能维持方面起关键作用,被视为CD4+CD25+调节性T细胞的特征性表面标记。已有研究发现FOXP3+调节性T细胞在恶性黑色素瘤、胃肠肿瘤、乳腺癌等肿瘤中明显增多,且与肿瘤分期和高死亡率有关。但是关于探讨其在皮肤良性肿瘤、癌前病变、恶性肿瘤皮损中的表达情况及意义的研究较少。 目的: 检测脂溢性角化、日光性角化、鲍恩病、鳞状细胞癌及正常人皮肤中FOXP3的表达情况,探讨其在正常人皮肤、皮肤良性肿瘤、癌前病变、恶性肿瘤皮损中表达的可能意义。 材料和方法: 1.收集齐鲁医院皮肤科近10年保存的经临床及病理确诊的73例表皮肿瘤蜡块,其中脂溢性角化20例、日光性角化19例、鲍恩病21例、鳞状细胞癌13例;取门诊手术室及整形美容外科切除正常皮肤标本13例,作为正常对照组;另取病理室保存的扁桃体石蜡标本,作为阳性对照组。 2.采用免疫组化方法检测FOXP3在不同表皮肿瘤及正常对照组中的表达情况。 3.应用SPSS13.0统计分析软件进行处理,表皮肿瘤各组与正常皮肤间FOXP3表达差异比较采用Mann-Whitney U检验;SK、AK、BD和SCC多组间比较采用单因素方差分析,多组间两两比较采用最小显著差值法(least-significant difference, LSD), P0.05为差异有统计学意义。 结果: 1. FOXP3在正常皮肤和表皮肿瘤的表达结果 FOXP3主要表达于真皮层淋巴细胞,胞核、胞浆均有阳性染色,为棕黄色或棕褐色。正常对照组、SK组、AK组和BD组部分标本能观察到FOXP3+淋巴细胞。而SCC组13例均能观察到FOXP3+淋巴细胞,其在肿瘤浸润淋巴细胞中呈灶状分布。在AK组、BD组、SCC组除真皮层,表皮细胞间亦可见FOXP3+表达的淋巴细胞。 2. FOXP3在不同表皮肿瘤中表达的阳性标记指数 表皮肿瘤皮损中FOXP3阳性标记指数均明显高于正常皮肤组织,差异具有统计学意义(P0.01)。SK组、AK组、BD组和SCC组间FOXP3 LI差异有统计学意义(P0.01);AK组FOXP3 LI高于SK组(P0.05);BD组、SCC组FOXP3LI均高于AK组(P0.05);SCC组FOXP3 LI高于BD组但差异无统计学意义(P0.05)。 结论: 1.肿瘤组织中浸润的淋巴细胞过多的表达FOXP3,可能抑制了效应性细T胞功能,削弱了其抗肿瘤免疫的作用。 2. FOXP3+淋巴细胞在表皮良性肿瘤,癌前病变,恶性肿瘤中的表达呈逐渐增高趋势,可能在表皮肿瘤的免疫逃逸中发挥了重要作用,促进了其发生发展或性质的转变。 3. FOXP3+淋巴细胞的表达在BD与SCC间差异无统计学意义,提示原位癌中的肿瘤细胞可能已经具备了某种免疫调节能力,开始分泌或表达趋化因子来招募越来越多的FOXP3+淋巴细胞,为癌症的更进一步发展提供了条件。
[Abstract]:Study Background: Previous studies have shown that cancer patients are in a state of tolerance or defect in both local and systemic immune function of the tumor, and the tumor must be carried out only after the immune surveillance of the escape body In order to develop, regulatory T cells are a kind of T-lymphocyte subpopulation with immunoregulation function, which have strong immunosuppression function and play a very important role in tumor immune escape The classical FOXP3 + CD4 + CD25 + regulatory T cell (CD4 + CD25 + regulatory T cells, CD4 + CD25 + Treg) is the most important group of cells in the T cell, but the immune response initiated by the autoantigen and the foreign antigen has an immunomodulating effect and is an important machine for maintaining the immune tolerance of the body. The transcription factor P3 (Foxp3), which is a member of the family of the forked transcription factors, plays a key role in the differentiation and development of CD4 + CD25 + regulatory T cells and is regarded as the characteristic form of CD4 + CD25 + regulatory T cells. The results showed that FOXP3 + regulatory T cells increased significantly in malignant melanoma, gastrointestinal tumor, breast cancer and other tumors, and it was associated with tumor staging and high death. The study of the expression and significance of its expression in the skin benign, pre-cancerous and malignant lesions of the skin. less Objective: To study the expression of FOXP3 in the skin of normal people, such as seborrheic keratosis, keratosis, Bowen's disease, squamous cell carcinoma and normal human skin. Expression of the lesions in the skin of the tumor Material and method:1. Collect 73 cases of epidermal tumor wax block preserved in the Department of Dermatology of Qilu Hospital for nearly 10 years, of which 20 cases of seborrheic keratosis and the keratosis of the sunlight 19 cases,21 cases of Bowen's disease,13 cases of squamous cell carcinoma,13 cases of normal skin specimens from the outpatient operating room and the plastic and cosmetic surgery, as the normal control group, and the other pathology The cell-preserved tonsil paraffin specimen was used as the positive control group.2. The immunohistochemistry method was used to detect F. 3. The expression of OXP3 in different epidermal and normal controls.3. The expression of FOXP3 between the groups of the epidermis and the normal skin was compared with the Mann-Whitney U test. The single-factor analysis of variance was used for the comparison between the groups of SK, AK, BD and SCC. -significant dif transfer There was a significant difference in the difference between P.05 and P.05. Significance. Results:1. The expression of FOXP3 in normal and epidermal tumors FOXP3 is mainly expressed in the lymphocytes of the dermis, the nucleus and the cytoplasm are stained with positive staining and are brown or yellow. The FXP3 + lymphocytes were observed in the normal control group, the SK group, the AK group and the BD group. FOXP3 + lymphocytes were observed in all the 13 cases of SCC group, and it was distributed in the tumor-infiltrating lymphocytes. In the AK group, the BD group, the SCC group and the dermis layer, the epidermal cells also The positive marker index of FOXP3 expression in different epidermal tumors was higher than that of normal skin tissue, and the difference was of statistical significance. (P0.01) The difference of FOXP3 LI between the group, the AK group, the BD group and the SCC group was statistically significant (P0.01), and the FOXP3 LI in the AK group was higher than that of the SK group (P0.05); and the group of the groups in the group B and the SCC group FOXP3L I are both high In the group of AK (P0.05), the FOXP3 LI in the SCC group was higher than that in the BD group, but the difference was not significant (P0.05). 1. Overexpression of FOXP3 in the infiltrating lymphocytes in the tumor tissue may inhibit the function of effector fine T cells and weaken the anti-tumor immune function.2. FOXP3 + lymphocytes are benign in the epidermis. The expression of the tumor, precancerous lesion and malignant tumor is gradually increasing, which can play an important role in the immune escape of the epidermal tumor, and promote the transformation of the development or the character of the tumor. No statistical significance, and it is suggested that the tumor in the carcinoma of the human body
【学位授予单位】:山东大学
【学位级别】:硕士
【学位授予年份】:2010
【分类号】:R739.5

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