5-氟尿嘧啶与顺铂联合诱导化疗方案对舌鳞状细胞癌多药耐药相关蛋白表达及预后的影响

发布时间：2018-05-31 11:37

本文选题：舌鳞状细胞癌 + 诱导化疗　；参考：《广西医科大学》2017年硕士论文

【摘要】：目的:研究5-氟尿嘧啶与顺铂联合诱导化疗方案舌鳞状细胞癌肿瘤组织中多药耐药相关蛋白1(MRP1)、多药耐药相关蛋白2(MRP2)、P糖蛋白(P-gp)表达情况,探讨5-氟尿嘧啶与顺铂联合(PF)化疗方案诱导治疗对舌鳞状细胞癌多药耐药相关蛋白的关系及预后的影响。方法:1、收集经病理确诊为舌鳞状细胞癌的患者82例,根据治疗方式不同分为:PF诱导方案化疗+手术治疗组,单纯手术治疗组,每组各41例,通过回顾性分析对比两组临床基线资料之间的关系。2、免疫组化SP法:检测82例舌鳞状细胞癌组织中MRP1、MRP2、P-gp三种耐药相关蛋白的表达情况,对比PF化疗+手术治疗组中化疗前、后上述指标表达的差异。3、Log-rank检验、Kaplan-Meier法及COX模型分析上述三种蛋白及临床病理相关指标与舌鳞状细胞癌患者预后生存时间的关系。结果:1、PF诱导化疗+手术治疗组和单纯手术治疗组的临床病理参数分析结果显示:两组间的性别、年龄、病变部位,TNM分期,病理分级,淋巴结转移,肿瘤大小,颈清方式,复发/转移资料匹配。两组病例治疗前活检标本的MRP1、MRP2、P-gp表达差异均无显著性(P0.05),提示两组之间具有可比性。2、PF诱导化疗后舌鳞状细胞癌中原发灶和区域淋巴结临床评价CR为1例(2.4%),PR为20例(48.7%),SD为19例(46.3%),PD为1例(2.5%),依据术后病理检查情况,达到总有效率(CR+PR)51.21%。3、PF化疗组诱导化疗前舌鳞状细胞癌组织中P-pg、MRP1和MRP2蛋白的阳性率分别为56.09%(23/41)、60.97%(25/41)和53.65%(22/41),经2个疗程化疗后TSCC组织中P-pg、MRP1和MRP2阳性率为70.73%(29/41)、78.05%(32/41)和51.22%(21/41)。其中P-pg、MRP1化疗前后阳性表达率差异均有显著性(P0.05)。4、Kaplan-Meier法、COX模型多因素结果分析显示PF诱导化疗+手术治疗组,P-gp的表达、临床分期是影响舌鳞状细胞癌预后的独立危险因素。结论:1、PF诱导化疗后舌鳞状细胞癌组织中P-gp及MRP1蛋白表达较化疗前呈上调趋势,提示该方案可诱导舌鳞状细胞癌耐药性产生。2、PF诱导化疗后,P-gp的表达、临床分期是舌鳞状细胞癌预后的独立危险因素。3、舌鳞状细胞癌经5-氟尿嘧啶与顺铂联合诱导化疗,可使肿瘤缩小,缓解肿瘤发展,但PF诱导化疗方案与单纯手术治疗两种方案相比,5年总体生存率无显著性差异。
[Abstract]:Objective: to study the expression of multidrug resistance-associated protein (MRP1P) and multidrug resistance-associated protein 2MRP2P glycoprotein (P-gp) in squamous cell carcinoma of tongue (TSCC) induced by 5-fluorouracil (5-FU) and cisplatin (cisplatin). To investigate the effect of 5-fluorouracil combined with cisplatin combined with PFN on the relationship and prognosis of multidrug resistance-associated protein in tongue squamous cell carcinoma. Methods 82 cases of squamous cell carcinoma of tongue diagnosed by pathology were collected and divided into two groups according to the different treatment methods: the chemotherapy group treated with 10% PF induction regimen and the simple operation group (41 cases in each group). The relationship between the clinical baseline data of the two groups was analyzed retrospectively. Immunohistochemical SP method was used to detect the expression of MRP1T MRP2P-gp in 82 cases of tongue squamous cell carcinoma, and to compare the expression of three kinds of drug resistance-associated proteins in the PF group before chemotherapy. Kaplan-Meier method and COX model were used to analyze the relationship between the three proteins and the clinicopathological parameters and the survival time of tongue squamous cell carcinoma patients. Results the clinicopathologic parameters of the two groups were as follows: sex, age, TNM stage, pathological grade, lymph node metastasis, tumor size, cervical clearance. Recurrence / metastasis data matched. There was no significant difference in the expression of P-gp between the two groups of biopsy specimens before treatment, suggesting that there was no significant difference in the expression of P-gp between the two groups. It suggested that the clinical evaluation of the primary focus and regional lymph nodes in the squamous cell carcinoma of tongue after chemotherapy induced by 2.2PF showed that the CR was 1 case, and the PR of 20 cases was 48.7%. 19 cases with PD of 46.3% were found to be 2. 5%, according to the pathological examination after operation, The positive rates of P-pgGN MRP1 and MRP2 protein in tongue squamous cell carcinoma before induction chemotherapy were 56.09 and 53.65%, respectively. The positive rates of P-pgG MRP1 and MRP2 in TSCC tissues were 70.7329 / 411 and 51.22 / 41, respectively, and 51.22% / 41, 51.22% / 41, respectively, after two courses of chemotherapy, the positive rates of P-pgGN MRP1 and MRP2 in TSCC tissues were 70.7329 / 411) and 51.2222% / 32 / 41, respectively.The positive rates of P-pgG MRP1 and MRP2 were 70.7375 / 41 and 51.22% / 32 / 41, respectively, and the positive rates of P-pgG MRP1 and MRP2 in TSCC tissues were 70.73 / 41 and 51.22% / 21 / 41, respectively. There were significant differences in the positive expression rates of P-pgtr MRP1 before and after chemotherapy. The multivariate analysis of the Cox model showed that the expression of P-gp in the PF induced chemotherapy group was an independent risk factor for the prognosis of tongue squamous cell carcinoma (TSCC), and the clinical stage was an independent risk factor for the prognosis of tongue squamous cell carcinoma (TSCC). Conclusion the expression of P-gp and MRP1 protein in squamous cell carcinoma of tongue after chemotherapy induced by 1: 1PF showed an up-regulation trend compared with that before chemotherapy. It suggested that this regimen could induce the expression of P-gp in squamous cell carcinoma of tongue after chemotherapy. Clinical stage is an independent risk factor for the prognosis of squamous cell carcinoma of tongue. Combined chemotherapy with 5-fluorouracil and cisplatin can reduce tumor size and relieve tumor development. However, there was no significant difference in 5-year overall survival rate between PF induced chemotherapy regimen and surgical therapy alone.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.86

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