【作者】 陈悦；

【导师】 邓觐云；

【作者基本信息】 南昌大学 ， 肿瘤学， 2010， 硕士

【摘要】 目的：探讨乳腺癌(breast carcinoma)细胞色素P450 1B1 (cytochrome P450 1B1, CYP1B1)及雌激素受体(ER)、孕激素受体(PR)表达情况与多西他赛体外药敏的关系,为指导多西他赛应用于乳腺癌的个体化治疗提供重要的理论依据。方法：1、收集41例乳腺癌患者手术切除的新鲜标本,立即用三磷酸腺苷-肿瘤细胞药敏试验(ATP-tumor chemosensitivity assay, ATP-TCA)进行多西他赛体外药敏检测。2、采用免疫组织化学链霉素抗生物素蛋白-过氧化物酶连接法(S-P法)对该41例乳腺癌患者的石蜡包埋标本进行CYP1B1及ER、PR蛋白表达检测。3、比较分析CYP1B1与ER、PR蛋白表达间的相互关系,以及CYP1B1、ER、PR表达与多西他赛体外药敏的关系。结果：1、41例乳腺癌标本中,多西他赛体外有效为18例(43.9%),体外无效为23例(56.1%)。2、41例乳腺癌患者中,CYP1B1阳性表达占78%(32/41),ER为46.3%(19/41),PR为43.9%(18/41)。ER、PR表达之间明显正相关(P<0.05)。CYP1B1阳性表达率在ER阳性组(73.7%)与阴性组(81.8%)无显著差异(P>0.05),但在PR阴性组的阳性表达显著高于PR阳性组(91.3%VS61.1%; P<0.05)。CYP1B1阳性表达还与淋巴结转移和临床分期正相关(P<0.05)。3、32例CYP1B1蛋白阳性表达组中,多西他赛体外有效11例(34.4%),9例CYP1B1阴性表达组中,多西他赛体外有效7例(77.8%),CYP1B1阳性表达者对多西他赛的敏感性明显低于阴性表达者(P<0.05)。结论：1、CYP1B1蛋白阳性表达可能与乳腺癌患者对多西他赛耐药相关。2、CYP1B1阳性表达与淋巴结转移和临床分期正相关,可能为乳腺癌患者预后不佳的重要指标。3、CYP1B1阳性表达与PR表达呈负相关,与ER表达无关。更多还原

【Abstract】 Objective:To determine the relationship between CYP1B1、ER、PR expression and sensitivity of breast cancer to docetaxel in vitro, providing important theoretical evidence to guide docetaxel’s individual chemotherapy in breast cancer field.Methods:1.41 fresh operative breast carcinoma samples were collected and immediately used to be tested the sensitivity to docetaxel with the method of ATP-tumor chemosensitivity assay.2. The expression of CYP1B1、ER、PR protein in 41 paraffin-embedded samples of breast cancer was determined through immunohistochemical analysis (S-P method).3. Analyze the relationship between CYP1B1 and ER、PR protein expression, these protein expression and sensitivity of breast carcinomas to docetaxel in vitro.Results:1. There were 18(43.9%) cases sensitive to docetaxel in the 41 breast carcinomas specimen, and still another 23(56.1%) resistant cases.2. The positive expression of CYP1B1 was 78%(32/41) in the 41 breast carcinomas specimen,and ER was 46.3%(18/41),PR was 43.9%(18/41).The positive rates of CYP1B1 expression had no correlation between ER positive or negative group (73.7%VS81.8%;P>0.05), but its positive rate was significant higher in PR negative group than the positive group(91.3%VS61.1%; P<0.05). Moreover, CYP1B1 was positive related with lymphatic metastasis and clinical stage.3. There were 11(34.4%) cases with sensitve to docetaxel in vitro in the 32 cases of CYP1B1-positive group, and 7(77.8%) sensitive cases in the 7 cases of CYP1B1-negative group. The sensitivity to docetaxel of CYP1B1-positive group was significantly lower than the negative group (P<0.05).Conclusions:1. CYP1B1-positive expression may be related to breast cancer’s resistance to docetaxel.2. CYP1B1 was positive related with lymphatic metastasis and clinical stage, which could be the important factor of poor prognosis of the patients with breast cancer.3. The positive rates of CYP1B1 expression had no correlation between ER positive or negative group, but its positive rate was significant higher in PR negative group than the positive group.更多还原