【作者】 高媛；

【导师】 王霞；

【作者基本信息】 青岛大学 ， 妇科肿瘤， 2008， 硕士

【摘要】 目的:研究上皮性卵巢肿瘤中BRCAl、Ki-67的表达,探讨其在原发性上皮性卵巢癌（Primary Epithelial Ovarian Cancer）发生、发展及预后中的临床意义。方法:联合应用组织芯片技术和免疫组化方法,检测BRCAl、Ki-67在62例原发性上皮性卵巢癌、14例交界性卵巢肿瘤、30例良性卵巢肿瘤中的表达。结果:1.上皮性卵巢癌组织中BRCA l蛋白的异常表达率（80.6%）明显高于交界性肿瘤（14.3%）和良性卵巢肿瘤（0%）,差别有高度统计学意义（P＜0.01）。卵巢癌组织中BRCAl的阳性表达率（59.7%）明显低于交界性肿瘤（92.9%）和良性卵巢肿瘤（100%）,差别有统计学意义（P＜0.05）。2.BRCAl蛋白在卵巢癌组织学分级差的G₃组阳性表达率（31.6%）明显低于G₁、G₂组（分别为78.6%、69.0%）,差别有统计学意义（P＜0.05）,G₁和G₂比较差别没有统计学意义（P＞0.05）。BRCAl蛋白的表达与卵巢癌病理类型、临床分期无关。3.Ki-67在卵巢癌、交界性肿瘤、良性肿瘤中的阳性率分别为72.6%、21.4%、0%。两两比较差别均有统计学意义（P＜0.05）。尤其Ki-67在卵巢癌强阳性表达率（53.2%）显著高于交界性肿瘤和良性肿瘤（均为0%）,差别有显著统计学意义（P＜0.01）。4.Ki-67在卵巢癌中、低分化G₂、G₃组中阳性表达率（分别为75.9%、94.7%）明显高于高分化G₁组（35.7%）,差别有统计学意义（P＜0.05）。在临床分期Ⅲ期Ⅳ期中阳性表达率（84.6%）明显高于Ⅰ期Ⅱ期（52.2%）,差别有统计学意义（P＜0.05）。Ki-67的表达与卵巢癌病理类型无关（P＞0.05）。5.卵巢癌中BRCAl蛋白和Ki-67蛋白的表达呈负相关（P＜0.05）。结论:1.BRCAl蛋白在卵巢良性肿瘤中高表达于细胞核,而在卵巢癌中表达降低且多误表达于细胞浆,提示BRCAl亚细胞定位异常及BRCAl的表达下调可能是诱发卵巢癌的原因之一。2.BRCAl的表达与卵巢癌组织学分级有关,与临床分期、病理类型无关。提示BRCAl蛋白表达降低预示着卵巢癌的恶性程度增加,BRCAl蛋白的表达水平可作为评估卵巢癌恶性程度的指标之一。3.Ki-67在良性卵巢肿瘤中阴性表达,在交界性肿瘤中表达增高,而在卵巢癌中高表达,说明Ki-67能客观反映肿瘤细胞的增殖能力,可作为鉴别卵巢肿瘤性质的理想指标。4.Ki-67的表达与卵巢癌组织学分级、临床分期有关,与卵巢癌病理类型无关。提示Ki-67的过度表达预示着卵巢癌的恶性进展。5.在卵巢癌中BRCAl和Ki-67蛋白的表达呈负相关。联合检测BRCAl,Ki-67表达情况可以为卵巢癌早期筛查、估计恶性程度、判断预后及指导治疗方面提供理论依据。更多还原

【Abstract】 Objective:To investigate the expression of BRCA1 and Ki-67 in epithelial ovarian tumor and the clinical significance in pathogenesis,progression and prognosis of primary epithelial ovarian cancer.Methods:Tissue microarray technology and immunohistochemical method was used to detect the expression of BRCA1 and Ki-67 in 62 cases of primary epithelial ovarian cancer、14 cases of borderline epithelial ovarian tumor and 30 cases of benign epithelial ovarian tumor.Results:①The abnormal expression rates of BRCA1 in epithelial ovarian cancer （80.6%） were significantly higher than that in borderline tumor（14.3%） and benign tumor（0%） of ovarian.The positive expression rates of BRCA1 in epithelial ovarian cancer（59.7%） were significantly lower than that in borderline tumor（92.9%） and benign tumor（100%） of ovarian.②The present data demonstrated that the expression of BRCA1 was not significantly correlated with surgical-pathologic staging and histological types of ovarian cancer（P＞0.05）,but correlated with pathologic grade of ovarian cancer （P＜0.05）.The expression of BRCA1 in G₃ was31.6%,which was remarkably reduced than in G₁,G₂（78.6%and 69.0%）.③Immunohitochemical analysis also showed that Ki-67 expressed increased in cancer（72.6%） than in borderline tumors（21.4%） or benign tumors（0%） of ovarian（P＜0.05）.Especially,the strong positive expression of Ki-67 was striking increased in ovarian cancer（53.2%） than in borderline ovarian tumor and benign ovarian tumor（0%）（P＜0.01）.④A strong association has been observed between the expression of Ki-67 and surgical-pathologic staging,pathologic grade of ovarian cancer（P＜0.05）,but not with hisological types（P＞0.05）.The expression of Ki-67 was decreased in stageⅠ～Ⅱ（52.2%） than inⅢ～Ⅳ（84.6%）.its levels were increased in grade G_2-3（75.9%and 94.7%） thanin G₁（35.7%）.⑤.Expression of BRCA1 was negatively correlated with expression of Ki-67. Conclusion:①In benign ovarian tumor,expression of BRCA1 was stained in cell nucleus.However,in primary epithelial ovarian cancer,expression of BRCA1 was abnormal,such as decrease or absent in nucleus and mislocated in cytoplasm.The results suggest that anormaly of BRCA1 protein expression may be an important event in pathogenesis of the epithelial ovarian cancer.②The expression of BRCA1 protein was correlated with pathologic grade of ovarian cancer,which indicated the level of BRCA1 protein expression may be an indicatrix to judge the malignant degree of ovarian cancer.③Ki-67 expressed increased in cancer than in borderline tumors and benign tumors of ovarian,which demonstrated that the expression of Ki-67 can reflect reproductive activity of malignant cell and may be an ideal indicatrix to discriminate the property of ovarian tumor.④A strong association has been observed between the expression of Ki-67 and surgical-pathologic staging,pathologic grade of ovarian cancer,which indicates cell hyperproliferation is an important mechanism during the evolution of the ovarian cancer. The expression of Ki-67 may be an indicatrix to judge the malignant extent of ovarian cancer.⑤There is a significantly inverted relationship between the expression of BRCA1 protein and that of Ki-67 protein.The conjoined detection of BRCA1 and Ki-67 protein may be helpful to estimate malignant extent,judge prognosis and guide therapy of ovarian cancer.更多还原