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应用眼眶淋巴瘤组织芯片检测P-gp、GST-π及LRP的表达及其临床意义

Significance and Quantitative Expression of P-glycoprotein、Glutathione-S-transferase-π and Lung Resistance Protein in the Orbital Lymphoma Tissue Microarray

【作者】 郭振峰

【导师】 孙丰源;

【作者基本信息】 天津医科大学 , 眼科学, 2011, 硕士

【摘要】 研究目的制作眼眶淋巴瘤组织芯片;利用免疫组织化学检测三种耐药蛋白在眼眶淋巴瘤中的表达情况,初步探索该病的复发及预后不良机制研究方法1收集2003年至2008年期间诊断为眼眶淋巴瘤及反应性淋巴增生患者的临床病理资料,并对病人进行随访。2制作眼眶淋巴瘤组织芯片。3应用免疫组织化学检测P-gp、GST-π、LRP在眼眶淋巴瘤中的表达。4应用SPSS13.0统计学软件对数据进行分析,以α=0.05为检验水准,P<0.05认为有统计学意义。研究结果1 50例眼眶淋巴瘤和17例眼眶反应性淋巴增生组织芯片经HE染色后,病理诊断结果与原取材的大组织诊断完全一致;有4例眼眶淋巴瘤在免疫组织化学的染色过程中一脱片,因此末对这4例标本的染色结果进行统计。2三种耐药蛋白,P-gp和GST-π在眼眶淋巴瘤和反应性淋巴增生组织芯片中有不同程度表达,LRP在两种组织中均为阴性表达。P-gp蛋白主要表达于细胞膜,在两种病变的阳性表达率为87.0%和35.3%,其差异有统计学意义;GST-π表达于细胞浆,在两种病变的阳性表达率为76.1%和41.2%,其差异有统计学意义。3 46例淋巴瘤:P-gp和GST-π这两种蛋白的阳性表达率在≥60岁和<60岁年龄组间、男女性别组间、≥2.5cm和<2.5cm肿瘤组间及≥1年和<1年发病时间组间均无统计学意义。4将有随访结果的35例眼眶淋巴瘤分为两组,即预后不良组和预后良好组;P-gp在两组间的表达率分别为85.7%和42.9%,其差异有统计学意义;GST-π在两组间的表达率分别为78.7%和38.1%,其差异有统计学意义。5 P-gp和GST-π在眼眶淋巴瘤中的表达呈正相关(P<0.05)。结论1眼眶淋巴瘤组织芯片省时快速,结果可靠,高效经济地研究了该肿瘤的多药耐药基因表达状况。2 P-gp在眼眶淋巴瘤和反应性淋巴增生组间阳性比率表达差异有统计学意义,说明P-gp对判断眼眶淋巴细胞性疾病的病变性质有一定价值;同时P-gp在眼眶淋巴瘤预后不良组和预后良好组间阳性率表达差异有统计学意义,说明P-gp可以预测眼眶淋巴瘤的预后。3 GST-π在眼眶淋巴瘤和反应性淋巴增生组间阳性率表达差异有统计学意义,说明P-gp对判断眼眶淋巴细胞性疾病的病理性质有一定意义;同时GST-π在眼眶淋巴瘤预后不良组和预后良好组间阳性率表达差异有统计学意义,说明GST-π可以预测眼眶淋巴瘤的预后4 LRP在眼眶淋巴瘤和反应性淋巴增生组均呈阴性表达,提示LRP与眼眶淋巴细胞性疾病的发生发展无明确相关性。5 P-gp和GST-π蛋白在眼眶淋巴瘤中的表达呈正相关,联合检测这两种指标可能对预测眼眶淋巴瘤预后有更大价值。

【Abstract】 ObjetiveWe produce orbital lymphoma tissue microarray and detect the three resistance protein in the orbital lymphoma tissues by Immunohistochemistry to explore the relapse and poor prognosis mechanism of the disease mechanismMethods1. Collect the clinical and pathological information of patients as orbital lymphoma and reactive lymphoid hyperplasia from 2003 to 2008 and make a follow up of all patients..2. Produce produce orbital lymphoma tissue microarray.3. Immunohistochemical staining was used to detect the expression of P-gp, GST-πand LRP in orbital lymphoma and reactive lymphoid hyperplasia.4. The data was analyzed by SPSS 17.0 statistical software. P<0.05 was regarded as the standard of statistical significance.Results1. The pathological diagnosis of the tissue microarray of fifty orbital lymphoma and seventeen reactive lymphoid hyperplasia is consistant with the original tissue. There are four orbital lymphoma off-chips in the process of Immunohistochemical staining and so we don’t cout their results.2. P-gp and GST-πexpressed in tissue microarray of orbital lymphoma and reactive lymphoid hyperplasia in different levels. LRP doesn’t expressed in the both tumors tissue microarray. P-gp maily expressed in the cell membrance. The P-gp expression rates are 87.0% and 64.7% in the two tumors tissue microarray and there is significant difference between them(P<0.05). GST-πmaily expressed in the cytoplasm. The GST-πexpression rates are 76.1% and 47.1% in the two tumors tissue microarray and there is significant difference between them(P<0.05).3. The expression of P-gp and GST-πhas nothing to do with ages, sexs, tumor size and course of disease in the orbital lymphoma. 4. We divided the orbital lymphoma wih follow-up results into two groups:poor prognosis group and good prognosis group. The P-gp expression rates are 85.7% and 42.9% in the two groups and there is significant difference between them(P<0.05). The GST-πexpression rates are 78.7% and 38.1% in the two groups and there is significant difference between them(P<0.05).5. The positive correlation was showed between protein expression levels of P-gp and GST-πin the orbital lymphoma.Conc|usion1.By orbital lymphoma tissue microarray we detect the MDR gene expression rapidly, reliably, efficiently and economically.2.The difference of P-gp expression between the orbital lymphoma and reactive lymphoid hyperplasia was statistically significant, which maybe demonstrate that P-gp can reflect the malignancy degree of the orbital lymphoid disease. Meanwhile, in the orbital lymphoma the difference of P-gp expression between the poor prognosis group and good prognosis group was statistically significant, which maybe demonstrate that P-gp can predict the prognosis of the orbital lymphoma.3.The difference of GST-πexpression between the orbital lymphoma and reactive lymphoid hyperplasia was statistically significant, which maybe demonstrate that GST-πcan reflect the malignancy degree of the orbital lymphoid disease. Meanwhile, in the orbital lymphoma the difference of GST-πexpression between the poor prognosis group and good prognosis group was statistically significant, which maybe demonstrate that GST-πcan predict the prognosis of the orbital lymphoma.4..The positive correlation was showed between protein expression levels of P-gp and GST-πin the orbital lymphoma, which demonstrate that combined detection of P-gp and GST-πmaybe contribute to predict the prognosis of the orbital lymphoma.

【关键词】 眼眶淋巴瘤P-gpGST-πLRP预后免疫组织化
【Key words】 orbital lymphomaP-gpGST-πLRPImmunohistochemistry
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