FOXP3在正常人皮膚和表皮腫瘤中的表達(dá)及意義
發(fā)布時(shí)間：2019-06-01 08:56
【摘要】： 研究背景： 以往的研究表明：癌癥患者在腫瘤局部和全身的免疫功能都處于耐受或缺陷狀態(tài),腫瘤必需在逃逸機(jī)體的免疫監(jiān)控之后才得以發(fā)展。調(diào)節(jié)性T細(xì)胞是一類(lèi)具有免疫調(diào)節(jié)功能的T淋巴細(xì)胞亞群,這類(lèi)細(xì)胞有較強(qiáng)的免疫抑制功能,在腫瘤免疫逃逸中起著十分重要的作用。雖然調(diào)節(jié)T細(xì)胞有多種類(lèi)型,但是經(jīng)典的FOXP3+CD4+CD25+調(diào)節(jié)性T細(xì)胞(CD4+CD25+regulatory T cells, CD4+CD25+Treg)是其中最主要的一群細(xì)胞,其對(duì)自身抗原和外來(lái)抗原引發(fā)的免疫反應(yīng)均具有免疫調(diào)節(jié)作用,是機(jī)體維持免疫耐受的重要機(jī)制之一。叉頭狀轉(zhuǎn)錄因子P3(forkhead--winged helix transcription factor-3, Foxp3)是叉頭狀轉(zhuǎn)錄因子家族中的一員,對(duì)CD4+CD25+調(diào)節(jié)性T細(xì)胞在分化發(fā)育、功能維持方面起關(guān)鍵作用,被視為CD4+CD25+調(diào)節(jié)性T細(xì)胞的特征性表面標(biāo)記。已有研究發(fā)現(xiàn)FOXP3+調(diào)節(jié)性T細(xì)胞在惡性黑色素瘤、胃腸腫瘤、乳腺癌等腫瘤中明顯增多,且與腫瘤分期和高死亡率有關(guān)。但是關(guān)于探討其在皮膚良性腫瘤、癌前病變、惡性腫瘤皮損中的表達(dá)情況及意義的研究較少。 目的： 檢測(cè)脂溢性角化、日光性角化、鮑恩病、鱗狀細(xì)胞癌及正常人皮膚中FOXP3的表達(dá)情況,探討其在正常人皮膚、皮膚良性腫瘤、癌前病變、惡性腫瘤皮損中表達(dá)的可能意義。 材料和方法： 1.收集齊魯醫(yī)院皮膚科近10年保存的經(jīng)臨床及病理確診的73例表皮腫瘤蠟塊,其中脂溢性角化20例、日光性角化19例、鮑恩病21例、鱗狀細(xì)胞癌13例；取門(mén)診手術(shù)室及整形美容外科切除正常皮膚標(biāo)本13例,作為正常對(duì)照組；另取病理室保存的扁桃體石蠟標(biāo)本,作為陽(yáng)性對(duì)照組。 2.采用免疫組化方法檢測(cè)FOXP3在不同表皮腫瘤及正常對(duì)照組中的表達(dá)情況。 3.應(yīng)用SPSS13.0統(tǒng)計(jì)分析軟件進(jìn)行處理,表皮腫瘤各組與正常皮膚間FOXP3表達(dá)差異比較采用Mann-Whitney U檢驗(yàn)；SK、AK、BD和SCC多組間比較采用單因素方差分析,多組間兩兩比較采用最小顯著差值法(least-significant difference, LSD), P0.05為差異有統(tǒng)計(jì)學(xué)意義。 結(jié)果： 1. FOXP3在正常皮膚和表皮腫瘤的表達(dá)結(jié)果 FOXP3主要表達(dá)于真皮層淋巴細(xì)胞,胞核、胞漿均有陽(yáng)性染色,為棕黃色或棕褐色。正常對(duì)照組、SK組、AK組和BD組部分標(biāo)本能觀察到FOXP3+淋巴細(xì)胞。而SCC組13例均能觀察到FOXP3+淋巴細(xì)胞,其在腫瘤浸潤(rùn)淋巴細(xì)胞中呈灶狀分布。在AK組、BD組、SCC組除真皮層,表皮細(xì)胞間亦可見(jiàn)FOXP3+表達(dá)的淋巴細(xì)胞。 2. FOXP3在不同表皮腫瘤中表達(dá)的陽(yáng)性標(biāo)記指數(shù) 表皮腫瘤皮損中FOXP3陽(yáng)性標(biāo)記指數(shù)均明顯高于正常皮膚組織,差異具有統(tǒng)計(jì)學(xué)意義(P0.01)。SK組、AK組、BD組和SCC組間FOXP3 LI差異有統(tǒng)計(jì)學(xué)意義(P0.01)；AK組FOXP3 LI高于SK組(P0.05)；BD組、SCC組FOXP3LI均高于AK組(P0.05)；SCC組FOXP3 LI高于BD組但差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論： 1.腫瘤組織中浸潤(rùn)的淋巴細(xì)胞過(guò)多的表達(dá)FOXP3,可能抑制了效應(yīng)性細(xì)T胞功能,削弱了其抗腫瘤免疫的作用。 2. FOXP3+淋巴細(xì)胞在表皮良性腫瘤,癌前病變,惡性腫瘤中的表達(dá)呈逐漸增高趨勢(shì),可能在表皮腫瘤的免疫逃逸中發(fā)揮了重要作用,促進(jìn)了其發(fā)生發(fā)展或性質(zhì)的轉(zhuǎn)變。 3. FOXP3+淋巴細(xì)胞的表達(dá)在BD與SCC間差異無(wú)統(tǒng)計(jì)學(xué)意義,提示原位癌中的腫瘤細(xì)胞可能已經(jīng)具備了某種免疫調(diào)節(jié)能力,開(kāi)始分泌或表達(dá)趨化因子來(lái)招募越來(lái)越多的FOXP3+淋巴細(xì)胞,為癌癥的更進(jìn)一步發(fā)展提供了條件。
[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
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類(lèi)號(hào)】：R739.5
[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
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類(lèi)號(hào)】：R739.5
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