【作者】 孙勇；

【导师】 付荣湛；

【作者基本信息】 山东大学 ， 外科学， 2009， 硕士

【摘要】 目的:原发性乳腺癌是女性常见的恶性肿瘤之一,化学药物治疗是乳腺癌治疗的重要组成部分。目前的诸多研究已明确肿瘤的多药耐药性(Multidrug-resistance,MDR)是导致临床化疗失败最主要的原因。现在认为细胞中的P-gp、LRP这两种蛋白表达可能与多种肿瘤的多药耐药相关。本文观察了P-gp和LRP在癌旁、乳腺癌中的表达情况及其与乳腺癌病理因素的关系,旨在探讨其在乳腺癌多药耐药中所起的作用及两者的相关性。材料与方法:本课题收集山东大学附属千佛山医院2007年7月至2009年1月诊治的浸润性乳腺癌40例,留取取癌组织和距癌边缘1 cm以上的癌旁腺体组织作为对照。采用搓网法获取乳腺癌手术切除标本制成的完整的单细胞悬液,采用流式细胞术对40例乳腺癌组织及相应癌旁组织中P-gp、LRP的表达情况进行定量分析。结果:1.浸润性乳腺癌组织P-gp、LRP的表达:乳腺癌组织P-gp的表达为(23.5±13.7)%,相应癌旁组织P-gp达为(5.1±5.0)%。经t检验,乳腺癌组织P-gp表达与相应癌旁组织差异有统计学意义(p＜0.05)。乳腺癌组织LRP的表达为(35.4±17..8)%,相应癌旁组织LRP达为(6.8±6.5)%。经t检验,乳腺癌组织LRP表达与相应癌旁组织差异有统计学意义(p＜0.05)。2.P-gp、LRP的表达与临床病理资料的比较:两种耐药蛋白的表达与患者的年龄、肿瘤大小、病理类型、组织学分级、临床分期和雌、孕激素受体均无相关性(p＞0.05)。有淋巴结转移组患者P-gp表达与无淋巴结转移组患者比较无显著差异(p＞0.05)。有淋巴结转移组患者LRP的表达为(38.8±19.3)%,无淋巴结转移组患者为(32.2±16.0)%。LRP表达在有淋巴结转移组患者显著高于无淋巴结转移组患者(p＜0.05)。3.P-gp、LRP表达的相互关系:Pearson相关分析显示,乳腺癌组织P-gp与LRP的表达间存在正相关性(p＜0.05)。结论:1.2种耐药蛋白在浸润性乳腺癌组织中的表达存在差别。2.LRP的表达与淋巴结转移状况有关且与P-gp表达呈正相关,可作为预测乳腺癌预后的指标。3.在乳腺癌组织的原发耐药中可有P-gp、LRP的共表达,联合检测P-gp、LRP的表达有望指导临床对乳腺癌化疗药物做出选择。更多还原

【Abstract】 Objective:Primary breast carcinoma is one of the most common malignances.Chemotherapy is one of important part of breast carcinoma’ therapy.It has been found that the multidrug-resistance(MDR) is the main reason that leads to failure of chemotherapy.P-gp、LRP have been proposed as correlation with multidrug-resistance.In this study,our aim is to understand the expression and significance of P-gp、LRP in breast carcinoma and the relationship of between the two drugresistance-associated proteins.Materials and Methods:We collected 40 specimens of breast carcinoma of Shandong provincal Qianfoshan hospital during the period from July 2007 to September 2009.Single-cell suspension with intact cellular membrane taken from operative specimens of breast carcinoma were prepared using rubbing-net technique. Flow Cytometry(FCM) was used to examine the expression of proteins P-gp and LRP in carcinoma tissues and corresponding para-carcinoma tissues.Results:1.The expressions of P-gp and LRP in carcinoma tissues and corresponding para-carcinoma tissues:In breast carcinoma their expression level of P-gp was(23.3±13.7)%.In corresponding para-carcinoma tissues,their expression level of P-gp was(5.1±5.0)%.The expression of P-gp was higher in breast carcinoma tissues than that in corresponding para-carcinoma tissues(p＜0.05).In breast carcinoma their expression level of LRP was(35.4±17.8)%.In corresponding para-carcinoma tissues,their expression level of LRP was(6.8±6.5)%.Their differences were obvious(p＜0.05).2.The expression of P-gp and and clinical-pathological data:There were not notable differences of two drug resistance related protein expressions in different ages,different tumor sizes,different pathological types,different clinical stages,estrogen receptor or progestin receptor negative and positive patients(p＞0.05).There was no notable difference of P-gp expression in lymph node metastasis negative and positive patients(p＞0.05).The expression of LRP was higher in lymph node metastasis positive patients than that in negative patients(p＜0.05).The expression of LRP was significantly associated with axillary node postive.3.The correlation among the expression of P-gp and LRP:The Pearson correlation analysis showed that there was a positive correlaion between the expression of P-gp and the expression of LRP(p＜0.05)Conclusions:1.The expressions of P-gp and LRP in breast carcinoma were different. 2.The expression of LRP in breast carcinoma was significantly associated with axillary node postive,which perhaps has a close relationship with metastasis of breast carcinoma.It can become a target in forecasting breast carcinoma prognosis.3.The co-expression of P-gp and LRP can be found in the primary drug resisitance of breast carcinoma.Measuring the expression of P-gp and LRP in breast carcinoma together might guide the choice of chemotherapy drugs.更多还原