乳腺癌新辅助化疗前后PD-L1的表达与肿瘤浸润免疫细胞及化疗疗效的相关性研究

发布时间：2018-03-03 10:37

本文选题：乳腺癌　切入点：新辅助化疗　出处：《西南医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:通过检测乳腺癌新辅助化疗前后程序性死亡配体1(PD-L1,Programmed death-ligand-1)的表达以及肿瘤局部微环境中浸润免疫细胞的浸润情况,分析其与乳腺癌患者临床病理特征的关系,探讨乳腺癌新辅助化疗前后PD-L1的表达与局部肿瘤浸润免疫细胞间的相关性及与新辅助化疗疗效的关系。方法:1.选取2014年1月—2016年6月西南医科大学附属医院乳腺外科接受新辅助化疗的浸润性乳腺癌95例,同时收集乳腺纤维腺瘤和正常乳腺组织各30例;2、完善乳腺彩超、乳腺钼靶、MRI、CT及全身骨显像等检查,根据患者临床、病理资料进行临床分期。以TAC方案作为乳腺癌新辅助化疗方案(环磷酰胺500mg/m2,吡柔比星50mg/m2,多西他赛75mg/m2,21天为一化疗周期),每化疗2-3周期后进行疗效评估,达临床完全缓解、部分缓解或者化疗2-3周期后无进展者行手术治疗;3、将新辅助化疗前后的肿瘤组织行免疫组化检测PD-L1、CD8和CD68,分析PD-L1的表达与患者临床病理特征的关系,PD-L1、CD8+T细胞和CD68+巨噬细胞间相关性以及与新辅助化疗疗效的关系,并采用SPSS17.0统计软件对数据进行统计分析,计数资料采用χ2检验,应用Spearman相关进行分类变量的相关性分析,多因素分析采用Logistic回归。结果:1.本实验中正常乳腺组织未检测到PD-L1表达,而乳腺纤维腺瘤中呈不表达或弱表达,在乳腺癌中表达明显升高,且明显高于正常乳腺组织和纤维腺瘤组织(P0.05);2.乳腺癌中PD-L1的表达与患者年龄、组织学分级未见相关性(P0.05),而与肿瘤大小、ER、PR、Her2、淋巴结转移显著相关,差异具有统计学意义(P0.05),且PD-L1阳性表达者T、N分期越高,主要在ER、PR、Her2阴性中表达;3.以TAC为新辅助化疗方案的化疗疗效与患者年龄、临床分期、组织学分级、分子分型、ER的表达不具有相关性(P0.05),而与PR、Her2的表达有显著相关性(P0.05),且PR、Her2阴性者化疗有效率更高;4.化疗前PD-L1的表达及化疗前后PD-L1表达的变化与化疗疗效具有相关性,化疗前肿瘤组织中CD8+T细胞及化疗前后浸润程度的变化也与化疗疗效具有相关性,差异均有统计学意义(P0.05),且当患者PD-L1阴性、CD8阳性时在化疗中获益更大,而本实验未显示CD68+巨噬细胞及化疗前后的变化与化疗疗效间有明显相关性(P0.05);5.在新辅助化疗前后PD-L1的表达与CD8+T细胞浸润呈负相关(r=-0.332,P=0.001),而CD68+巨噬细胞浸润度与肿瘤细胞表面表达的PD-L1不具有明显相关性(P0.05)。结论:1.在乳腺正常组织、纤维腺瘤组织、浸润性癌组织中PD-L1阳性表达呈上升趋势,且PD-L1表达阳性者与T、N分期、ER、PR、Her2的表达有显著相关性;其中PD-L1表达阳性者其T、N分期越高,并以ER、PR、Her2阴性患者为主。2.以TAC为新辅助化疗方案时,患者年龄、临床分期、组织学分级、分子分型、CD68+巨噬细胞与新辅助化疗疗效未见明显相关性,而PR、Her2、PD-L1、CD8+T细胞与新辅助化疗疗效有显著相关性,且PD-L1阴性、CD8+T细胞阳性的患者在化疗中更有获益更大,二者可以作为TAC新辅助化疗方案中近期疗效预测的独立影响因素。3.乳腺癌中PD-L1的表达与CD8+T细胞的浸润程度呈负相关关系,而与CD68+巨噬细胞无明显相关性。
[Abstract]:Objective: through neoadjuvant chemotherapy for breast cancer detection programmed death ligand 1 (PD-L1, Programmed, death-ligand-1) infiltration of infiltrating immune cells and expression of tumor microenvironment, analyze its relationship with clinicopathological characteristics of patients with breast cancer, to explore the relationship between PD-L1 expression and tumor infiltrating immune cells and the correlation between the efficacy of neoadjuvant chemotherapy before and after neoadjuvant chemotherapy for breast cancer. Methods: 1. Affiliated Hospital from January 2014 to June 2016 Southwest Medical University breast surgery receiving neoadjuvant chemotherapy in invasive breast carcinoma in 95 cases, while collecting breast fibroadenoma and normal breast tissues in 30 cases; 2, improve breast ultrasound, mammography, MRI, CT and the whole body bone imaging examination, according to the clinical and pathological data were in clinical stage. TAC regimen as neoadjuvant chemotherapy on breast cancer (cyclophosphamide, 500mg/m2, pyridine Doxorubicin docetaxel 50mg/m2, 75mg/m2,21 days for a cycle of chemotherapy), the clinical efficacy was evaluated every 2-3 cycles of chemotherapy, clinical complete remission, partial remission or progression free after 2-3 cycles of chemotherapy were treated with operation; 3, the tumor immune group before and after neoadjuvant chemotherapy in the detection of PD-L1, CD8 and CD68, the relationship between analysis, PD-L1 expression and the clinicopathological characteristics of patients with PD-L1, CD8+T cells and CD68+ macrophages and the correlation between the relationship with the efficacy of neoadjuvant chemotherapy, and using SPSS17.0 statistical software for statistical analysis, count data using 2 test, correlation analysis using Spearman correlation classification variables, multivariate analysis using Logistic regression. Results: 1. normal breast tissue in this experiment did not detect the expression of PD-L1, and breast fibroadenoma was not expression or weak expression, the expression significantly increased in breast cancer, and was significantly higher In normal breast tissues and fibroadenoma (P0.05); the expression of PD-L1 2. in breast cancer patients with age, histological grade (P0.05), but no correlation with tumor size, ER, PR, Her2, is significantly related to lymph node metastasis, the difference was statistically significant (P0.05), and the positive expression of PD-L1 T, N the higher the stage, mainly in ER, PR, Her2 negative expression; 3. to TAC for the efficacy of chemotherapy and neoadjuvant chemotherapy in patients age, clinical stage, histological grade, molecular typing, ER expression has no correlation (P0.05), and PR, there was significant correlation between the expression of Her2 (P0.05) and, PR, Her2 negative effective chemotherapy rate; there is a correlation between the expression of PD-L1 and efficacy of chemotherapy before and after chemotherapy and the expression of 4. PD-L1 before chemotherapy, chemotherapy and chemotherapy before and after the change of CD8+T cells in tumor tissue infiltration also has correlation with the efficacy of chemotherapy, were statistically significant Meaning (P0.05), and when the patients with PD-L1 negative, CD8 positive in chemotherapy of greater benefit, but this experiment did not show changes and curative effect of chemotherapy before and after chemotherapy and CD68+ macrophages had significant correlation (P0.05; 5.) before and after neoadjuvant chemotherapy in PD-L1 expression and CD8+T cell infiltration showed a negative correlation (r=-0.332. P=0.001 and CD68+), macrophage infiltration and tumor cell surface expression of PD-L1 has no obvious correlation (P0.05). Conclusion: 1. in normal breast tissue, breast tissues, the positive expression of PD-L1 in invasive carcinoma showed a rising trend, and the expression of PD-L1 and T, ER, PR, N stage, there was a significant correlation between the expression of Her2; the expression of PD-L1 positive and the T, the higher the stage of N, and in ER, PR, Her2 negative patients.2. neoadjuvant chemotherapy for patients with TAC, age, clinical stage, histological grade, molecular typing, and neoadjuvant CD68+ macrophages There is no significant correlation between the curative effect, while PR, Her2, PD-L1, CD8+T cells have significant correlation with the efficacy of neoadjuvant chemotherapy, and PD-L1 negative patients, CD8+T positive cells in chemotherapy more benefit more, there was a negative correlation between the infiltration degree of independent effect on the expression of PD-L1.3. in breast cancer cells and CD8+T two can as of TAC neoadjuvant chemotherapy curative effect prediction, but had no correlation with CD68+ macrophages.

【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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