甲状腺乳头状癌中BRAF突变蛋白表达与NIS蛋白表达的相关研究

发布时间：2018-05-06 04:10

本文选题：甲状腺乳头状癌 + NIS蛋白　；参考：《青岛大学》2017年硕士论文

【摘要】：目的:通过研究山东省青岛地区PTC患者的BRAF突变蛋白(鼠类肉瘤滤过性毒菌致癌同源体B1)、钠碘转运体(sodium/iodide symporter,NIS)蛋白的表达情况,探讨了NIS、BRAF突变蛋白之间的关系,及其和PTC肿瘤参数之间的关系,同时分析了~(131)I治疗效果与BRAF突变蛋白、NIS蛋白及病理参数的关系,为PTC的诊断、治疗、预后提供临床指导意义。方法:应用NIS、BRAF单克隆抗体及免疫组化法检测青岛大学附属医院(黄岛院区)在2015年1月至2015年12月期间,术后的留档蜡块60例,包括PTC 40例、结甲20例,分别行BRAF突变蛋白及NIS蛋白的免疫组化。(1)分析PTC及结甲患者中NIS、BRAF突变蛋白的表达;(2)分析40例PTC中NIS、BRAF突变蛋白表达情况与肿瘤参数、~(131)I治疗效果的相关性。(3)将PTC按照癌旁组织不同分为结甲组、正常组,进一步分析两组之间NIS、BRAF突变蛋白、~(131)I治疗效果及病理参数等的差异。结果:1.在40例PTC中,BRAF突变蛋白阳性表达33例(82.5%),在20例结甲组织中,无阳性表达,经卡方检验,差异有显著意义(p0.05);2.在40例PTC患者中NIS蛋白表达的有33例(82.5%),20例结甲组织中有18例为阳性(90%),经卡方检验差异无意义(P0.05);3.在33例NIS蛋白表达的PTC组织中,2例(6.1%)在胞膜上,31例(93.9%)在胞质中,18例NIS蛋白表达的结甲组织中,17例在胞膜上表达,1例在胞质中表达,经Fisher检验,差异有明显统计学意义(p0.001);4.在40例PTC组织中,经spearman相关性分析,认为BRAF、NIS具有正相关关系(r=0.596,p0.01);5.在40例PTC组织中,经卡方检验,性别间BRAF突变蛋白表达差异有意义(p=0.089);6.在40例PTC组织中,经spearman相关分析,认为~(131)I治疗效果与BRAF突变蛋白表达呈负相关(r=-0.225,p=0.028);7.PTC分组中,经t检验,显示正常组与结甲组中~(131)I治疗效果及病灶数的差异有显著意义(P=0.025,p0.001)。结论:1.山东省青岛地区散发PTC患者中BRAF突变蛋白检测率较高,结甲患者无阳性表达。应用免疫组化法去检测BRAF突变蛋白的表达情况,可以为甲状腺结节性质的判断提供临床参考价值。2.NIS转运蛋白在PTC及结甲患者中,其量及强度无明显的差别。碘治疗的效果可能与NIS蛋白定位有关,错误定位可能引起治疗抵抗或失败。3.碘治疗效果可能受肿瘤旁组织影响,肿瘤旁为正常组织比结甲患者效果好。4.在常规检查基础上联合检测NIS、BRAF突变蛋白的表达,可为PTC患者诊断、~(131)I治疗及疾病的预后提供更高的临床参考价值。
[Abstract]:Objective: to study the expression of BRAF mutant protein (B1T, sodium iodide symporter) in PTC patients with sarcoma leucosarcoma, and to explore the relationship between NIS-BRAF mutation protein. The relationship between PTC and tumor parameters was also analyzed, and the relationship between the therapeutic effect and the BRAF mutant protein and pathological parameters were analyzed, which provided clinical guidance for the diagnosis, treatment and prognosis of PTC. Methods: NIS-BRAF monoclonal antibody and immunohistochemical method were used to detect 60 cases of wax blocks, including 40 cases of PTC and 20 cases of armour formation, from January 2015 to December 2015 in the affiliated Hospital of Qingdao University (Huangdao Hospital). Immunohistochemical analysis of BRAF mutant protein and NIS protein was performed in 40 cases of PTC. The expression of NIS-BRAF mutant protein was analyzed by immunohistochemistry. The expression of NIS-BRAF mutant protein was analyzed in 40 cases of PTC. The relationship between the expression of NIS-BRAF mutant protein and the therapeutic effect of tumor parameter, Angii 131I, was analyzed respectively. 3) the relationship between the expression of NIS-BRAF mutant protein and the therapeutic effect of NIS-BRAF in 40 cases of PTC was analyzed. Paracancerous tissues were divided into knot A group. In the normal group, the difference of the therapeutic effect and pathological parameters of NIS-BRAF mutant protein (NIS-BRAF) was further analyzed between the two groups. The result is 1: 1. In 40 cases of PTC, 33 cases had positive expression of BRAF mutant protein, 33 cases had positive expression of BRAF protein, but in 20 cases of thyroid tissue, there was no positive expression. The difference was significant by chi-square test. Of the 40 cases of PTC, there were 33 cases with positive expression of NIS protein, 18 of 20 cases of thyroid tissue were positive, there was no significant difference between them by chi-square test (P 0.05). In 33 cases of PTC with NIS protein expression, 2 cases (6. 1) were expressed on the membrane of 31 cases (93. 9%) in the cytoplasm of 18 cases of NIS protein expression, 17 cases were expressed on the membrane of 1 case in the cytoplasm. By Fisher test, the difference was statistically significant (P 0. 001 4). In 40 cases of PTC, spearman correlation analysis showed that BRAFN had a positive correlation with 0.596nis, p0.01a. In 40 cases of PTC, it was found by chi-square test that there was significant difference in the expression of BRAF mutant protein between sexes. In 40 cases of PTC, the results of spearman correlation analysis showed that there was a negative correlation between the therapeutic effect and the expression of BRAF mutant protein. The t test showed that there was a significant difference in the therapeutic effect and the number of lesions between the normal group and the nodular group. Conclusion 1. The detection rate of BRAF mutation protein was higher in sporadic PTC patients in Qingdao, Shandong province. Immunohistochemical method was used to detect the expression of BRAF mutant protein. 2. There was no significant difference in the quantity and intensity of NIS transporter in patients with PTC and thyroid nodule. The effect of iodine therapy may be related to the localization of NIS protein, and false localization may cause resistance or failure of treatment. The effect of iodine therapy may be affected by paraneoplastic tissue. The combined detection of NIS-BRAF mutant protein on the basis of routine examination can provide a higher clinical reference value for the diagnosis of PTC patients and the prognosis of the disease.
【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】：R736.1

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