碘难治性分化型甲状腺癌中NIS、OCT4和CD133表达的研究分析

发布时间：2018-05-27 10:32

本文选题：碘难治 + 甲状腺癌　；参考：《山东大学》2017年硕士论文

【摘要】：目的甲状腺癌是内分泌系统发病率最高的恶性肿瘤,虽然分化型甲状腺癌患者大部分都有良好的预后,但是依然有5%的分化型甲状腺癌的患者出现了远处转移,2/3的远处转移的患者和未分化型甲状腺癌一样,失去了对碘的摄取能力,这部分发生远处转移失去摄碘能力的分化型甲状腺癌被称为碘难治性分化型甲状腺癌(Radioiodine Refractory Thyroid Cancer,RAI-R DTC)。碘难治性分化型甲状腺癌患者预后较差,和大部分预后良好的分化型甲状腺癌区别巨大。本研究对碘难治性甲状腺癌患者病理组织进行搜集,对山东省齐鲁医院2002-2015年间行131I治疗,并符合《美国甲状腺协会2015年(American Thyroid Association,ATA)成人甲状腺结节和分化型甲状腺癌管理指南》中对于碘难治性甲状腺癌诊断的患者,对这部分患者的病理组织进行NIS、OCT4和CD133的免疫组化表达分析。探索碘难治型分化型甲状腺癌对放射碘治疗不敏感的分子病理机制,为碘难治分化型甲状腺癌的进一步治疗提供新的思路。方法搜集山东大学齐鲁医院2002-2015年间进行131I治疗的病人资料,选取符合《美国甲状腺协会2015年(American Thyroid Association,ATA)成人甲状腺结节和分化型甲状腺管理指南》中对于碘难治性分化型甲状腺癌的诊断标准,搜集这部分患者的病理组织标本。根据文献报导,NIS可能是造成碘难治患者对放射治疗不敏感的原因,选取NIS为目标蛋白进行研究。有证据显示,OCT4基因对于维持细胞多能性具有重要作用,与肿瘤细胞的恶性生物学特点和传统治疗抵抗性之间有一定关系,因此在本研究中把OCT4蛋白作为研究的目标之一。肿瘤干细胞学说的提出,让人们对肿瘤发生和发展有了新的认识,有研究指出,CD133为生物学标志的肿瘤干细胞对传统的化疗和放疗具有抵抗作用,因此在本研究中,选取CD133为研究目标。对患者的病理组织行目标蛋白的免疫组化染色分析,探究与同位素碘治疗不敏感之间的相关性。结果1.NIS在碘难治远处转移DTC中和对照组中的表达NIS表达在甲状腺滤泡的胞浆,细胞核未见表达(图1)。RAI-RDTC组NIS的阳性表达率为57.14%,RAIDTC组和正常对照组NIS的阳性表达率都达到了100%。最终的免疫组化评分显示,RAI-RDTC组为4.29±1.77,RAIDTC组为9.57±1.57,正常对照组10.14±0.94,RAI-RDTC组中NIS的阳性表达率明显低于RAIDTC组和正常对照组。免疫组化评分结果显示,RAI-RDTC组NIS表达明显少于RAI DTC组和正常对照组,RAI DTC组和正常对照组之间则无明显差异(表2)。2.0CT4在碘难治远处转移DTC和对照组中的表达在正常对照组没有观察到OCT4蛋白的表达,在RAI-R DTC和RAI DTC组,OCT4表达在甲状腺滤泡细胞和癌灶细胞的细胞核,胞浆不表达(图1)。在RAI-R DTC和RAI DTC组,OCT4的阳性表达率都高达100%,且最终的免疫组化评分组间没有统计学差异。3,CD133在碘难治远处转移DTC中和对照组中的表达在RAI-RDTC组中CD133散在表达在甲状腺滤泡细胞和癌灶细胞的胞浆和膜上。在RAI-RDTC组CD133的阳性表达率为71.43%,在RAI DTC组CD133的阳性表达率为42.85%,正常(阴性)对照组,未观察到CD133表达。最终的免疫组化评分 RAI-RDTC组为6.86±2.14,RAIDTC 组为 1.71 ±0.92(表1),RAI-R DTC组CD133的阳性表达率和免疫组化评分分都较RAI DTC组和正常对照组明显升高(图1.P0.05)。结论1.碘难治性分化型甲状腺癌背后的可能原因之一是NIS的表达降低,从而导致细胞从血液向细胞内转运的碘减少,对碘的摄取和蓄积能力降低;2.CD133在碘难治性DTC患者的病理组织中相对于对照组表达明显升高。3.OCT4虽然在正常甲状腺结节组织中的未检测到表达,但是在RAI-R DTC组和RAI DTC组中都显示高表达,提示OCT4可能不是造成碘同位素治疗不敏感的主要原因,但是对于甲状腺癌的发生发展有一定意义。
[Abstract]:Objective thyroid cancer is the highest incidence of malignant neoplasm in the endocrine system. Although most of the patients with differentiated thyroid cancer have good prognosis, 5% of the patients with differentiated thyroid cancer still have distant metastasis. The patients with distant metastases of 2/3 and undifferentiated thyroid cancer have lost the ability to absorb iodine. Differentiated thyroid carcinoma that partially metastases and loses iodine uptake is called Radioiodine Refractory Thyroid Cancer (RAI-R DTC). The prognosis of patients with iodized differentiated thyroid cancer is poor and is very different from that of most well differentiated thyroid cancers. The pathological tissue of patients with adenocarcinoma was collected and treated with 131I in Qilu Hospital of Shandong province for 2002-2015 years. It was in line with < 2015 (American Thyroid Association, ATA) adult thyroid nodule and differentiated thyroid cancer management guide > for the diagnosis of iodine refractory thyroid cancer, and the pathology of this part of the patients. The immunohistochemical expression analysis of NIS, OCT4 and CD133 was carried out to explore the molecular pathological mechanism of iodine refractory differentiated thyroid carcinoma which was insensitive to radioiodine treatment, providing a new idea for further treatment of iodine refractory differentiated thyroid cancer. Methods the data of patients with 131I treatment in Qilu Hospital of Shandong University were collected for 2002-2015 years. Select the diagnostic criteria for iodine refractory differentiated thyroid carcinoma in accordance with the American Thyroid Association (ATA) Association (ATA) adult thyroid nodule and differentiated thyroid management guide, and collect the pathological tissue specimens of this part of the patients. According to the literature, NIS may be a radiation therapy for patients with iodine refractory. The cause of insensitivity is to select NIS as the target protein. There is evidence that the OCT4 gene plays an important role in maintaining cell pluriability, and has a certain relationship with the malignant biological characteristics of the tumor cells and the traditional treatment resistance. Therefore, the OCT4 protein is one of the research goals in this study. It is suggested that people have a new understanding of the occurrence and development of tumor. It is pointed out that the tumor stem cells with CD133 as a biological marker are resistant to traditional chemotherapy and radiotherapy. Therefore, in this study, CD133 is selected as the research target. The immunohistochemical staining analysis of the target protein of the pathological tissue of the patients is used to explore and explore the isotope iodine. The correlation between treatment insensitivity. Results 1.NIS expression in DTC and control group was expressed in the cytoplasm of thyroid follicular, the nucleus was not expressed in the nucleus of thyroid follicular, and the positive expression rate of NIS in group.RAI-RDTC was 57.14%. The positive expression rate of NIS in group RAIDTC and normal control group reached the final immunohistochemical score of 100%.. The results showed that the RAI-RDTC group was 4.29 + 1.77, the RAIDTC group was 9.57 + 1.57 and the normal control group was 10.14 0.94. The positive expression rate of NIS in the RAI-RDTC group was significantly lower than that in the RAIDTC group and the normal control group. The immunohistochemical score showed that the NIS expression in the RAI-RDTC group was significantly less than that in the RAI DTC group and the normal control group, and there was no significant difference between the RAI DTC group and the normal control group. The expression of.2.0CT4 in DTC and control group was not observed in normal control group. In the normal control group, the expression of OCT4 protein was not observed. In the group of RAI-R DTC and RAI DTC, OCT4 was expressed in the nuclei of the thyroid follicle cells and cancer cells, and the cytoplasm was not expressed (Fig. 1). In RAI-R DTC and RAI DTC groups, the positive expression rate was up to 100%, and the most of them were in the RAI-R DTC and RAI DTC groups. There was no statistical difference between the final immunohistochemical score groups.3, the expression of CD133 in DTC and the control group in the iodine refractory distant metastasis, CD133 scattered in the cytoplasm and membrane of the thyroid follicle cells and cancer cells in the RAI-RDTC group. The positive expression rate of CD133 in the RAI-RDTC group was 71.43%, and the positive expression rate of CD133 in RAI DTC group was 42.85%, In the normal (negative) control group, the expression of CD133 was not observed. The final immunohistochemical score in the RAI-RDTC group was 6.86 + 2.14, the RAIDTC group was 1.71 + 0.92 (Table 1). The positive and immunohistochemical scores of CD133 in the RAI-R DTC group were significantly higher than those in the RAI DTC group and the normal control group (Fig. 1.P0.05). Conclusion behind the conclusion of 1. iodine refractory differentiated thyroid carcinoma One of the possible reasons is the decrease in the expression of NIS, which leads to the decrease of the iodized iodine from the blood to the cell and the decrease in the uptake and accumulation of iodine; the expression of 2.CD133 in the pathological tissue of the iodized DTC patients is significantly higher than that of the control group, although the expression in the normal thyroid gland nodules is not detected, but the expression of.3.OCT4 is not detected, but the expression of the cells is not detected in the normal thyroid nodule tissue. High expression in both RAI-R DTC and RAI DTC groups suggests that OCT4 may not be the main cause of insensitivity to iodine isotopes, but it is of certain significance for the development of thyroid cancer.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R736.1

【参考文献】