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

【摘要】：目的:通過(guò)檢測(cè)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(dá)以及腫瘤局部微環(huán)境中浸潤(rùn)免疫細(xì)胞的浸潤(rùn)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(dá)與局部腫瘤浸潤(rùn)免疫細(xì)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(xué)附屬醫(yī)院乳腺外科接受新輔助化療的浸潤(rùn)性乳腺癌95例,同時(shí)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(jìn)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(jìn)行療效評(píng)估,達(dá)臨床完全緩解、部分緩解或者化療2-3周期后無(wú)進(jìn)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(cè)PD-L1、CD8和CD68,分析PD-L1的表達(dá)與患者臨床病理特征的關(guān)系,PD-L1、CD8+T細(xì)胞和CD68+巨噬細(xì)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(jì)軟件對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析,計(jì)數(shù)資料采用χ2檢驗(yàn),應(yīng)用Spearman相關(guān)進(jìn)行分類(lèi)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(shí)驗(yàn)中正常乳腺組織未檢測(cè)到PD-L1表達(dá),而乳腺纖維腺瘤中呈不表達(dá)或弱表達(dá),在乳腺癌中表達(dá)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(dá)與患者年齡、組織學(xué)分級(jí)未見(jiàn)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(jì)學(xué)意義(P0.05),且PD-L1陽(yáng)性表達(dá)者T、N分期越高,主要在ER、PR、Her2陰性中表達(dá);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(xué)分級(jí)、分子分型、ER的表達(dá)不具有相關(guān)性(P0.05),而與PR、Her2的表達(dá)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(dá)及化療前后PD-L1表達(dá)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(xì)胞及化療前后浸潤(rùn)程度的變化也與化療療效具有相關(guān)性,差異均有統(tǒng)計(jì)學(xué)意義(P0.05),且當(dāng)患者PD-L1陰性、CD8陽(yáng)性時(shí)在化療中獲益更大,而本實(shí)驗(yàn)未顯示CD68+巨噬細(xì)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(dá)與CD8+T細(xì)胞浸潤(rùn)呈負(fù)相關(guān)(r=-0.332,P=0.001),而CD68+巨噬細(xì)胞浸潤(rùn)度與腫瘤細(xì)胞表面表達(dá)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(rùn)性癌組織中PD-L1陽(yáng)性表達(dá)呈上升趨勢(shì),且PD-L1表達(dá)陽(yáng)性者與T、N分期、ER、PR、Her2的表達(dá)有顯著相關(guān)性;其中PD-L1表達(dá)陽(yáng)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(shí),患者年齡、臨床分期、組織學(xué)分級(jí)、分子分型、CD68+巨噬細(xì)胞與新輔助化療療效未見(jiàn)明顯相關(guān)性,而PR、Her2、PD-L1、CD8+T細(xì)胞與新輔助化療療效有顯著相關(guān)性,且PD-L1陰性、CD8+T細(xì)胞陽(yáng)性的患者在化療中更有獲益更大,二者可以作為T(mén)AC新輔助化療方案中近期療效預(yù)測(cè)的獨(dú)立影響因素。3.乳腺癌中PD-L1的表達(dá)與CD8+T細(xì)胞的浸潤(rùn)程度呈負(fù)相關(guān)關(guān)系,而與CD68+巨噬細(xì)胞無(wú)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(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R737.9

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本文編號(hào)：1560679