本文選題：乳腺腫瘤 + 腫瘤相關(guān)巨噬細(xì)胞��； 參考：《安徽醫(yī)科大學(xué)》2016年碩士論文

【摘要】：目的：比較腫瘤相關(guān)巨噬細(xì)胞(tumor associated macrophages，，TAMs)和M2型TAMs在乳腺癌組織中的浸潤特點,并對其進(jìn)行計數(shù)。檢測乳腺癌組織中富含半胱氨酸的酸性分泌蛋白(secreted protein acidic and rich in cysteine, SPARC)的表達(dá),分析TAMs、M2型TAMs及SPARC蛋白與乳腺癌患者臨床病理特征及預(yù)后的關(guān)系。探討TAMs及M2型TAMs的浸潤和SPARC蛋白表達(dá)在乳腺癌中的生物學(xué)意義。方法：1、運用免疫組織化學(xué)染色技術(shù)檢測153例乳腺癌和30例乳腺良性病變組織中CD68、CD206、stabilin-1和SPARC的蛋白。2、以CD68+作為TAMs的標(biāo)記,CD68+/CD206+作為M2型TAMs的標(biāo)記,運用免疫熒光雙標(biāo)法檢測CD68/CD206、CD68/stabilin-1和CD206/stabilin-1在20例乳腺癌組織中的共表達(dá)。觀察stabilin-1+TAMs免疫表型,并分析CD68、CD206、stabilin-1和SPARC的表達(dá)與患者臨床病理特征及預(yù)后的關(guān)系。結(jié)果：1、乳腺癌組織中TAMs的浸潤密度明顯高于乳腺良性病變組織(P0.001)。乳腺癌組織中TAMs的浸潤密度與ER、PR陰性表達(dá)及Ki-67高表達(dá)有關(guān)(P=0.009,P=0.007,P=0.003)；乳腺癌四種分子分型中TAMs的浸潤密度不盡相同(P=0.02)。TAMs的浸潤密度與患者年齡、組織學(xué)分級、腫瘤直徑、淋巴結(jié)分期及HER-2表達(dá)狀態(tài)均無關(guān)。2、M2型TAMs在乳腺良性病變組織中浸潤密度明顯低于乳腺癌組織中的浸潤密度(P0.001)。乳腺癌組織中M2型TAMs的高密度浸潤與腫瘤直徑增大及淋巴結(jié)分期升高有關(guān)(P=0.001,P=0.017)；并與ER、PR陰性表達(dá)、HER-2陽性表達(dá)及Ki-67高表達(dá)有關(guān)(P=0.001,P=0.025,P=0.024,P=0.014);乳腺癌四種分子分型中M2型TAMs的浸潤密度不盡相同(P=-0.009)。而與年齡及組織學(xué)分級無關(guān)。3、stabilin-1+TAMs在乳腺癌組織中的浸潤密度明顯高于乳腺良性病變組織(P0.001)。 stabilin-1+TAMs高密度浸潤與腫瘤直徑增大、淋巴結(jié)分期升高及臨床分期升高有關(guān)(P均≤0.001)。而與患者年齡、組織學(xué)分及激素表達(dá)狀態(tài)均無關(guān)(P均0.05)。4、SPARC蛋白在乳腺癌組織中的陽性表達(dá)率明顯低于乳腺良性組織(P=0.003)。SPARC在乳腺癌組織中的低表達(dá)與淋巴結(jié)分期和臨床分期升高有關(guān)(P0.001,P=0.001)；隨腫瘤直徑增加,SPARC蛋白在乳腺癌組織中的低表達(dá)呈上升趨勢,但差異不具有統(tǒng)計學(xué)意義(P=0.070)。與患者年齡、組織學(xué)分級及激素表達(dá)狀態(tài)均無關(guān)(P均0.05)。SPARC與TAMs無相關(guān)性(r=0.039,P=0.632)；與M2型TAMs呈明顯負(fù)相關(guān)(r=-0.268,P=0.001)；與stabilin-1+TAMs亦呈明顯負(fù)相關(guān)(r=-0.241,P=0.003)。5、免疫熒光雙標(biāo)結(jié)果顯示,所有CD206+TAMs均表達(dá)CD68,僅50%左右CD68+TAMs表達(dá)CD206。所有stabilin-1+TAMs均表達(dá)CD68,但僅30%左右CD68+TAMs表達(dá)stabilin-1。所有stabilin-1+TAMs均表達(dá)CD206,約65.0%左右CD206+TAMs表達(dá)stabilin-1。 M2型TAMs與TAMs呈正相關(guān)(r=0.246,P=0.002)。stabilin-1+TAMs與TAMs無相關(guān)性(r=0.149,P=0.066)；與M2型TAMs呈明顯正相關(guān)(r=0.521,P0.001)。6、生存分析：M2型TAMs高密度浸潤與患者無病生存時間(disease free survival,DFS)及總生存時間(overall survival, OS)降低有關(guān)(P=0.020,P=0.005),而TAMs、 stabilin-1+TAMs及SPARC的表達(dá)均與之無關(guān)(P均0.05)。結(jié)論：1、乳腺癌組織中可見多量巨噬細(xì)胞浸潤,近半數(shù)表現(xiàn)為M2型極化方向,非激素依賴型和高增殖活性乳腺癌中尤為顯著。M2型TAMs高密度浸潤提示乳腺癌預(yù)后不良。2、stabilin-1+TAMs可能是M2型TAMs的一個亞型。3、SPARC蛋白可能作為乳腺癌分期和間質(zhì)巨噬細(xì)胞極化方向的生物學(xué)標(biāo)志物,它們可能共同影響乳腺癌的進(jìn)展和預(yù)后。
[Abstract]:Objective: To compare the infiltration characteristics of tumor associated macrophages (TAMs) and M2 type TAMs in breast cancer tissues and to count the expression of cysteine rich acid secreting proteins in breast cancer tissues (secreted protein acidic and rich in) The relationship between protein and the clinicopathological features and prognosis of breast cancer patients. The biological significance of TAMs and M2 type TAMs infiltration and SPARC protein expression in breast cancer. Methods: 1. Immunohistochemical staining was used to detect the protein.2 of CD68, CD206, stabilin-1 and SPARC in 153 cases of breast cancer and 30 cases of benign breast lesions, with CD68+. As a marker of TAMs, CD68+/CD206+ was used as a marker of M2 type TAMs. The co expression of CD68/CD206, CD68/stabilin-1 and CD206/stabilin-1 in 20 breast cancer tissues was detected by immunofluorescence double labeling. The immunophenotype of stabilin-1+TAMs was observed and the expression of CD68, CD206, stabilin-1 and SPARC was analyzed with the clinicopathological features and prognosis of the patients. Results: 1, the infiltration density of TAMs in breast cancer tissues was significantly higher than that of benign breast lesions (P0.001). The infiltration density of TAMs in breast cancer tissues was related to ER, PR negative expression and Ki-67 high expression (P=0.009, P=0.007, P=0.003); the infiltration density of TAMs in the four molecular types of breast cancer was different (P=0.02) and the density of.TAMs. The age, histological grade, tumor diameter, lymph node staging and HER-2 expression were not related to.2. The infiltration density of M2 type TAMs in benign breast lesions was significantly lower than that in breast cancer tissue (P0.001). The high density infiltration of M2 type TAMs in breast cancer tissues was associated with increased tumor diameter and increased lymph node staging (P=0.001, P=0.017); it was associated with ER, PR negative expression, HER-2 positive expression and high expression of Ki-67 (P=0.001, P=0.025, P=0.024, P=0.014). The M2 TAMs infiltration density of the four types of breast cancer was different (P=-0.009). P0.001. Stabilin-1+TAMs high density infiltration was associated with increased tumor diameter, increased lymph node staging and increased clinical staging (P < 0.001). But it was not associated with age, histological and hormone expression (P 0.05).4, and the positive expression rate of SPARC protein in breast cancer tissues was significantly lower than that of breast benign tissue (P=0. 003) the low expression of.SPARC in breast cancer tissues was associated with lymph node staging and higher clinical stage (P0.001, P=0.001). With the increase of the diameter of the tumor, the low expression of SPARC protein in breast cancer tissues increased, but the difference was not statistically significant (P=0.070). It was not related to the age of the patients, the histological grade and the state of the hormone expression (P all). .05) there is no correlation between.SPARC and TAMs (r=0.039, P=0.632); there is a significant negative correlation with M2 type TAMs (r=-0.268, P=0.001), and a negative correlation with stabilin-1+TAMs (r=-0.241, P=0.003). Left and right CD68+TAMs expression stabilin-1. all stabilin-1+TAMs expressed CD206, about 65% CD206+TAMs expressed stabilin-1. M2 TAMs and TAMs positive correlation (r=0.246, P=0.002). Disease free survival, DFS) and total survival time (overall survival, OS) decreased (P=0.020, P=0.005), but TAMs, stabilin-1+TAMs, and SPARC were all independent of it (all 0.05). Conclusion: 1, breast cancer tissue is seen in multiple macrophage infiltration, nearly half of the expression of polarization in the direction of polarization, non hormone dependent .M2 type TAMs high density infiltration suggests poor prognosis in breast cancer, and stabilin-1+TAMs may be a subtype of.3 in M2 type TAMs. SPARC protein may be a biological marker for breast cancer staging and polarization of interstitial macrophages, and they may affect the progression and prognosis of breast cancer together.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R737.9

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 孫孝媛;于國華;張居民;;乳腺癌組織SPARC和MMP-2表達(dá)相關(guān)性研究[J];中華腫瘤防治雜志;2015年09期

2 徐東旭;徐璐;李彥君;李朝輝;李智;滕月娥;;SPARC蛋白在乳腺癌組織中的表達(dá)及臨床意義[J];中國醫(yī)科大學(xué)學(xué)報;2014年06期

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