
【摘要】 目的 检测抑凋亡蛋白Survivin及多药耐药基因mdr1的表达蛋白P糖蛋白(Pgp)在卵巢上皮性癌中的表达,分析其在卵巢癌化学治疗耐药中的作用及与临床病理学特征间的关系。方法 应用免疫组织化学技术SP法检测8例正常卵巢组织、16例良性上皮性卵巢肿瘤、46例上皮性卵巢癌(浆液性癌28例、粘液性癌12例、内膜样癌6例)组织中的Survivin、Pgp蛋白的表达情况。结果 Survivin、Pgp蛋白在卵巢癌组织中阳性表达率分别为60.9%和34.8%,显著高于良性上皮性卵巢肿瘤组织31.3%、0%和正常卵巢组织(阴性)(P<0.05)。Survivin蛋白在Ⅲ-Ⅳ期恶性上皮性卵巢肿瘤组中的阳性表达高于Ⅰ-Ⅱ期肿瘤组(P<0.05);在低分化恶性上皮性卵巢肿瘤组织中的阳性表达高于中、高分化肿瘤组,有显著性差异(P<0.05),但与肿瘤组织类型无关。Survivin与Pgp在恶性上皮性卵巢肿瘤组中存在共同表达,卡方检验P<0.05,呈正性相关。结论 卵巢癌存在原发性耐药,而由Survivin高表达引起的凋亡抑制在卵巢癌多药耐药的发生中起一定作用。
【关键词】 卵巢肿瘤;多药耐药;P-糖蛋白;Survivin蛋白;免疫组织化学
The expression of survivin and Pgp proteins in epithelial ovarian carcinoma and its relationship with multidrug resistance in ovarian carcinoma
ABSTRACT: Objective To detect the expression of inhibitor of apoptosis protein survivin and mdr1 gene protein Pgp in ovarian epithelial carcinoma, and analyze their functions of drug resistance in chemotherapy and the relationship with pathological characteristics. Methods We detected the expression of survivin and mdr1 proteins in 8 cases of normal ovarian tissues, 16 cases of benign epithelial ovarian tumor tissues and 46 cases of epithelial ovarian cancerous tissues (28 cases of serous cystadenocarcinoma, 12 cases of mucinous cystadenocarcinoma, and 6 cases of endometrioid carcinoma) with immunohistochemistry. Results The positive rate of survivin and mdr1 proteins in ovarian cancerous tissues was 60.9% and 34.8%, respectively, which was significantly higher than that in benign epithelial ovarian tumor tissues (31.3% and 0%) and normal ovarian tissues (negative) (P<0.05).In epithelial ovarian carcinoma group, the level of survivin expression in stage Ⅲ-Ⅳ was significantly higher than that in stage Ⅰ~Ⅱ, and the positive rate in low differential epithelial ovarian carcinoma tissues was higher than in medium and high differential epithelial ovarian carcinoma tissues (P<0.05). There was no significant difference among different pathological types. There was coexpression of survivin and mdr1 in ovarian epithelial carcinoma, and positive correlation was seen for survivin and mdr1 in chisquare test. Conclusion Primary drug resistance exists in ovarian carcinoma. The abnormal survivin gene expression in ovarian cancerous tissues might induce apoptosis suppression, which might play a role in primary drug resistance and multiple drug resistance in ovarian carcinoma chemotherapy.
KEY WORDS: ovarian neoplasm; multidrug resistance; Pgp; survivin; immunohistochemistry
卵巢癌化学多药耐药(multidrug resistance, MDR)的研究既是热点问题,又是难点问题。目前认为多药耐药基因mdrl的表达产物P糖蛋白(Pgp)高表达是产生MDR的主要原因,Pgp是化疗耐药的最有力的指标,可用于预测肿瘤患者耐药[1]。而最新研究发现肿瘤细胞对凋亡的敏感性也是影响化疗效果的关键因素,本文旨在研究产生耐药的这两种不同机理之间内在联系,为探明肿瘤细胞多药耐药的详尽机制提供一些实验依据。
1 材料与方法
1.1 材料来源及分组 选取本院1999年1月至2004年8月送检的卵巢癌手术标本存档蜡块46例,组织学类型:浆液性囊腺癌27例,黏液性囊腺癌13例,子宫内膜样癌6例;病理分化程度:中、高分化组2