肿瘤相关巨噬细胞与富含半胱氨酸的酸性分泌蛋白SPARC在乳腺癌中的作用及意义

发布时间：2018-06-24 10:15

  本文选题：乳腺肿瘤 + 肿瘤相关巨噬细胞　； 参考：《安徽医科大学》2016年硕士论文

【摘要】：目的：比较肿瘤相关巨噬细胞(tumor associated macrophages，，TAMs)和M2型TAMs在乳腺癌组织中的浸润特点,并对其进行计数。检测乳腺癌组织中富含半胱氨酸的酸性分泌蛋白(secreted protein acidic and rich in cysteine, SPARC)的表达,分析TAMs、M2型TAMs及SPARC蛋白与乳腺癌患者临床病理特征及预后的关系。探讨TAMs及M2型TAMs的浸润和SPARC蛋白表达在乳腺癌中的生物学意义。方法：1、运用免疫组织化学染色技术检测153例乳腺癌和30例乳腺良性病变组织中CD68、CD206、stabilin-1和SPARC的蛋白。2、以CD68+作为TAMs的标记,CD68+/CD206+作为M2型TAMs的标记,运用免疫荧光双标法检测CD68/CD206、CD68/stabilin-1和CD206/stabilin-1在20例乳腺癌组织中的共表达。观察stabilin-1+TAMs免疫表型,并分析CD68、CD206、stabilin-1和SPARC的表达与患者临床病理特征及预后的关系。结果：1、乳腺癌组织中TAMs的浸润密度明显高于乳腺良性病变组织(P0.001)。乳腺癌组织中TAMs的浸润密度与ER、PR阴性表达及Ki-67高表达有关(P=0.009,P=0.007,P=0.003)；乳腺癌四种分子分型中TAMs的浸润密度不尽相同(P=0.02)。TAMs的浸润密度与患者年龄、组织学分级、肿瘤直径、淋巴结分期及HER-2表达状态均无关。2、M2型TAMs在乳腺良性病变组织中浸润密度明显低于乳腺癌组织中的浸润密度(P0.001)。乳腺癌组织中M2型TAMs的高密度浸润与肿瘤直径增大及淋巴结分期升高有关(P=0.001,P=0.017)；并与ER、PR阴性表达、HER-2阳性表达及Ki-67高表达有关(P=0.001,P=0.025,P=0.024,P=0.014);乳腺癌四种分子分型中M2型TAMs的浸润密度不尽相同(P=-0.009)。而与年龄及组织学分级无关。3、stabilin-1+TAMs在乳腺癌组织中的浸润密度明显高于乳腺良性病变组织(P0.001)。 stabilin-1+TAMs高密度浸润与肿瘤直径增大、淋巴结分期升高及临床分期升高有关(P均≤0.001)。而与患者年龄、组织学分及激素表达状态均无关(P均0.05)。4、SPARC蛋白在乳腺癌组织中的阳性表达率明显低于乳腺良性组织(P=0.003)。SPARC在乳腺癌组织中的低表达与淋巴结分期和临床分期升高有关(P0.001,P=0.001)；随肿瘤直径增加,SPARC蛋白在乳腺癌组织中的低表达呈上升趋势,但差异不具有统计学意义(P=0.070)。与患者年龄、组织学分级及激素表达状态均无关(P均0.05)。SPARC与TAMs无相关性(r=0.039,P=0.632)；与M2型TAMs呈明显负相关(r=-0.268,P=0.001)；与stabilin-1+TAMs亦呈明显负相关(r=-0.241,P=0.003)。5、免疫荧光双标结果显示,所有CD206+TAMs均表达CD68,仅50%左右CD68+TAMs表达CD206。所有stabilin-1+TAMs均表达CD68,但仅30%左右CD68+TAMs表达stabilin-1。所有stabilin-1+TAMs均表达CD206,约65.0%左右CD206+TAMs表达stabilin-1。 M2型TAMs与TAMs呈正相关(r=0.246,P=0.002)。stabilin-1+TAMs与TAMs无相关性(r=0.149,P=0.066)；与M2型TAMs呈明显正相关(r=0.521,P0.001)。6、生存分析：M2型TAMs高密度浸润与患者无病生存时间(disease free survival,DFS)及总生存时间(overall survival, OS)降低有关(P=0.020,P=0.005),而TAMs、 stabilin-1+TAMs及SPARC的表达均与之无关(P均0.05)。结论：1、乳腺癌组织中可见多量巨噬细胞浸润,近半数表现为M2型极化方向,非激素依赖型和高增殖活性乳腺癌中尤为显著。M2型TAMs高密度浸润提示乳腺癌预后不良。2、stabilin-1+TAMs可能是M2型TAMs的一个亚型。3、SPARC蛋白可能作为乳腺癌分期和间质巨噬细胞极化方向的生物学标志物,它们可能共同影响乳腺癌的进展和预后。
[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.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.9

【参考文献】

相关期刊论文 前2条

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2 徐东旭;徐璐;李彦君;李朝辉;李智;滕月娥;;SPARC蛋白在乳腺癌组织中的表达及临床意义[J];中国医科大学学报;2014年06期

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