本文選題：乳腺癌　切入點：新輔助化療　出處：《西南醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:通過檢測乳腺癌新輔助化療前后程序性死亡配體1(PD-L1,Programmed death-ligand-1)的表達以及腫瘤局部微環(huán)境中浸潤免疫細胞的浸潤情況,分析其與乳腺癌患者臨床病理特征的關(guān)系,探討乳腺癌新輔助化療前后PD-L1的表達與局部腫瘤浸潤免疫細胞間的相關(guān)性及與新輔助化療療效的關(guān)系。方法:1.選取2014年1月—2016年6月西南醫(yī)科大學附屬醫(yī)院乳腺外科接受新輔助化療的浸潤性乳腺癌95例,同時收集乳腺纖維腺瘤和正常乳腺組織各30例;2、完善乳腺彩超、乳腺鉬靶、MRI、CT及全身骨顯像等檢查,根據(jù)患者臨床、病理資料進行臨床分期。以TAC方案作為乳腺癌新輔助化療方案(環(huán)磷酰胺500mg/m2,吡柔比星50mg/m2,多西他賽75mg/m2,21天為一化療周期),每化療2-3周期后進行療效評估,達臨床完全緩解、部分緩解或者化療2-3周期后無進展者行手術(shù)治療;3、將新輔助化療前后的腫瘤組織行免疫組化檢測PD-L1、CD8和CD68,分析PD-L1的表達與患者臨床病理特征的關(guān)系,PD-L1、CD8+T細胞和CD68+巨噬細胞間相關(guān)性以及與新輔助化療療效的關(guān)系,并采用SPSS17.0統(tǒng)計軟件對數(shù)據(jù)進行統(tǒng)計分析,計數(shù)資料采用χ2檢驗,應(yīng)用Spearman相關(guān)進行分類變量的相關(guān)性分析,多因素分析采用Logistic回歸。結(jié)果:1.本實驗中正常乳腺組織未檢測到PD-L1表達,而乳腺纖維腺瘤中呈不表達或弱表達,在乳腺癌中表達明顯升高,且明顯高于正常乳腺組織和纖維腺瘤組織(P0.05);2.乳腺癌中PD-L1的表達與患者年齡、組織學分級未見相關(guān)性(P0.05),而與腫瘤大小、ER、PR、Her2、淋巴結(jié)轉(zhuǎn)移顯著相關(guān),差異具有統(tǒng)計學意義(P0.05),且PD-L1陽性表達者T、N分期越高,主要在ER、PR、Her2陰性中表達;3.以TAC為新輔助化療方案的化療療效與患者年齡、臨床分期、組織學分級、分子分型、ER的表達不具有相關(guān)性(P0.05),而與PR、Her2的表達有顯著相關(guān)性(P0.05),且PR、Her2陰性者化療有效率更高;4.化療前PD-L1的表達及化療前后PD-L1表達的變化與化療療效具有相關(guān)性,化療前腫瘤組織中CD8+T細胞及化療前后浸潤程度的變化也與化療療效具有相關(guān)性,差異均有統(tǒng)計學意義(P0.05),且當患者PD-L1陰性、CD8陽性時在化療中獲益更大,而本實驗未顯示CD68+巨噬細胞及化療前后的變化與化療療效間有明顯相關(guān)性(P0.05);5.在新輔助化療前后PD-L1的表達與CD8+T細胞浸潤呈負相關(guān)(r=-0.332,P=0.001),而CD68+巨噬細胞浸潤度與腫瘤細胞表面表達的PD-L1不具有明顯相關(guān)性(P0.05)。結(jié)論:1.在乳腺正常組織、纖維腺瘤組織、浸潤性癌組織中PD-L1陽性表達呈上升趨勢,且PD-L1表達陽性者與T、N分期、ER、PR、Her2的表達有顯著相關(guān)性;其中PD-L1表達陽性者其T、N分期越高,并以ER、PR、Her2陰性患者為主。2.以TAC為新輔助化療方案時,患者年齡、臨床分期、組織學分級、分子分型、CD68+巨噬細胞與新輔助化療療效未見明顯相關(guān)性,而PR、Her2、PD-L1、CD8+T細胞與新輔助化療療效有顯著相關(guān)性,且PD-L1陰性、CD8+T細胞陽性的患者在化療中更有獲益更大,二者可以作為TAC新輔助化療方案中近期療效預測的獨立影響因素。3.乳腺癌中PD-L1的表達與CD8+T細胞的浸潤程度呈負相關(guān)關(guān)系,而與CD68+巨噬細胞無明顯相關(guān)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.

【學位授予單位】：西南醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R737.9

【參考文獻】

相關(guān)期刊論文 前2條

1 王冰;王紅梅;徐方云;閔衛(wèi)平;;樹突狀細胞與腫瘤免疫[J];中國細胞生物學學報;2013年11期

2 邢傳平,劉斌,董亮;免疫組織化學標記結(jié)果的判斷方法[J];中華病理學雜志;2001年04期

相關(guān)博士學位論文 前1條

1 劉引;乳腺癌新輔助化療后腫瘤浸潤免疫細胞及其與患者預后的相關(guān)性[D];復旦大學;2013年

相關(guān)碩士學位論文 前1條

1 趙亞寧;腫瘤浸潤淋巴細胞與乳腺癌新輔助化療療效相關(guān)性的Meta分析[D];吉林大學;2016年

，

本文編號：1560679