PDCD4、Survivin、NF-κB与Nrf2在乳房外Paget病中的表达和相关性研究

发布时间：2018-05-08 04:12

本文选题：乳房外Paget病 + PDCD4　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:乳房外Paget病(Extramammary Paget’s disease EMPD)于1989年由Crocker首次报道,是一种相对少见的皮肤恶性肿瘤,其组织学来源仍存在争议,本病好发于老年人,常见于肛门、外生殖器区域,皮损呈湿疹样外观,组织病理可见Paget细胞。肿瘤的形成往往伴有抑癌基因的失活和癌基因的表达上调;而炎症与肿瘤的关系也越来越受到重视,炎症反应可改变病变部位的微环境、增加细胞突变的概率,促使肿瘤的发生。NF-κB、Nrf2信号通路不但在氧化应激与炎性反应中扮演着重要角色,在一些恶性肿瘤中,也发现有NF-κB、Nrf2的表达。该实验通过免疫组织化学的方法,检测抑癌基因PDCD4、癌基因Survivin及NF-κB、Nrf2在EMPD皮损及正常组织中的表达情况,探讨PDCD4、Survivin、NF-κB及Nrf2在EMPD发生、发展中的作用。方法:选取沧州市中心医院皮肤科2000年1月-2014年5月间经病理证实的EMPD组织30例,另选取腋窝处正常组织20例为对照组,采用免疫组化技术,综合统计染色强度及染色阳性率,运用SPSS17.0统计软件处理数据,比较病变组织及正常组织中PDCD4、Survivin、NF-κB及Nrf2的阳性表达率之间的差异,采用χ2检验,把具有统计学意义显著性差异的临界值设定为P0.05。PDCD4、Survivin、NF-κB及Nrf2相关性采用Pearson相关分析。结果:1 PDCD4在EMPD组织中阳性率为23.3%,在正常组织中阳性率为100%,两者相比较,有显著差异(P0.05),Survivin在EMPD组织中的阳性率为80%,在正常组织中未见表达,两者相比较,有显著差异(P0.05),NF-κB在EMPD组织中的阳性率为70%,在正常组织中未见表达,两者相比较,有显著差异(P0.05),Nrf2在EMPD组织中的阳性率为73.3%,在正常组织中的阳性率是10%,两者相比较,有显著差异(P0.05)。2 NF-κB在Survivin阳性和阴性患者中的阳性率分别是83.3%和33.3%,两者间差异有统计学意义(r=0.452,P=0.013),Nrf2在Survivin阳性和阴性患者中的阳性率分别是79.2%和33.3%,两者间差异有统计学意义(r=0.4,P=0.028)。3 PDCD4在Survivin阳性和阴性患者中的阳性率分别是12.1%和66.7%,两者间差异有统计学意义(r=-0.512,P=0.005),PDCD4在NF-κB阳性和阴性患者中的阳性率分别是4.8%和66.7%,两者间差异有统计学意义(r=-0.671,P=0.001),PDCD4在Nrf2阳性和阴性患者中的阳性率分别是9.1%和62.5%,两者间差异有统计学意义(r=-0.588,P=0.002)。结论:1 PDCD4蛋白在乳房外Paget病组织中的表达明显低于在正常组织中的表达。2 Survivin、NF-κB和Nrf2蛋白在乳房外Paget病组织中的表达明显高于在正常组织中的表达。3 Survivin蛋白与NF-κB、Nrf2蛋白在乳房外Paget病组织中的表达呈正相关。4 PDCD4蛋白与Survivin、NF-κB、Nrf2蛋白在乳房外Paget病组织中的表达呈负相关。5抑癌基因PDCD4、癌基因Survivin与NF-κB、Nrf2参与了乳房外Paget病的发生、发展,并表明,炎症反应可能在乳房外Paget病形成过程中有重要的作用。6 Survivin、NF-κB及Nrf2蛋白可联合作为免疫组化指标,辅助乳房外Paget病的诊断,并且可以协助明确手术后切缘情况。
[Abstract]:Objective: Extramammary Paget 's disease EMPD (Paget' s disease EMPD) was first reported by Crocker in 1989. It is a relatively rare malignant tumor of the skin. Its histological origin is still controversial. This disease occurs in the elderly, common in the anus, the external genitals area, the skin lesions are eczema like appearance, histopathologically, Paget cells. Tumor shape is seen. The inactivation of the tumor suppressor gene and the up-regulated expression of the oncogene are often up-regulated, and the relationship between inflammation and tumor is becoming more and more important. The inflammatory response can change the microenvironment of the lesion, increase the probability of cell mutation and promote the occurrence of.NF- kappa B in the tumor, and the Nrf2 signaling pathway not only plays an important role in oxidative stress and inflammatory response, but also plays an important role in oxidative stress and inflammatory response. In some malignant tumors, the expression of NF- kappa B, Nrf2 was also found. This experiment was used to detect the expression of tumor suppressor gene PDCD4, Survivin and NF- kappa B, Nrf2 in EMPD skin lesions and normal tissues by immunohistochemistry. The role of PDCD4, Survivin, NF- kappa, and development was explored. Methods: Cangzhou city center medicine 30 cases of EMPD, which were confirmed by pathology in the hospital department of Dermatology, January 2000 -2014 years, and 20 cases of normal tissue at the axilla were selected as the control group. The immunohistochemical technique was used to calculate the staining intensity and positive rate of dyeing. The data were processed by SPSS17.0 statistics software to compare the positive of PDCD4, Survivin, NF- kappa B and Nrf2 in the pathological and normal tissues. The difference between the sex expression rate, using the chi 2 test, set the critical value of statistically significant difference to P0.05.PDCD4, Survivin, NF- kappa B and Nrf2 correlation using Pearson correlation analysis. Results: the positive rate of 1 PDCD4 in EMPD tissue was 23.3%, and the Zhongyang sex rate in normal tissues was 100%, and there were significant differences (P0.05), Surv, Surv. The positive rate of ivin in EMPD tissues was 80%, and there was no expression in normal tissues. There were significant differences (P0.05). The positive rate of NF- kappa B in EMPD tissues was 70%, and there was no expression in normal tissues. There was a significant difference between the two groups (P0.05), the positive rate of Nrf2 in EMPD tissues was 73.3%, and the positive rate in normal tissues was 10%, The positive rates of P0.05.2 NF- kappa B in Survivin positive and negative patients were 83.3% and 33.3%, respectively, and the difference between them was statistically significant (r=0.452, P=0.013). The positive rates of Nrf2 in the positive and negative patients were 79.2% and 33.3%, respectively, and there was a significant difference between the two (r=0.4, P=0.028).3. The positive rates in Survivin positive and negative patients were 12.1% and 66.7%, respectively, and the differences were statistically significant (r=-0.512, P=0.005). The positive rates of PDCD4 in NF- kappa B positive and negative patients were 4.8% and 66.7% respectively (r=-0.671, P= 0.001), and the positive rates of PDCD4 in Nrf2 positive and negative patients were statistically significant. The difference between 9.1% and 62.5% was statistically significant (r=-0.588, P=0.002). Conclusion: the expression of 1 PDCD4 protein in external Paget disease was significantly lower than that in normal tissue, and the expression of NF- kappa B and Nrf2 protein in the external mammary Paget disease was significantly higher than that in normal tissues. The expression of kappa B, Nrf2 protein in Paget disease tissues is positively related to the.4 PDCD4 protein and Survivin, NF- kappa B, and the expression of Nrf2 protein in the external mammary Paget disease is negatively related to the.5 tumor suppressor gene PDCD4, and the oncogene is involved in the occurrence and development of the external mammary gland disease. There is an important role in the formation of.6 Survivin, NF- kappa B and Nrf2 protein can be combined as an immunohistochemical marker, assisting the diagnosis of Paget disease outside the breast, and can help to clarify the postoperative margin of the resection.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.5

【参考文献】