【作者】 黄春梅；

【导师】 史惠蓉； 赵先兰；

【作者基本信息】 郑州大学 ， 肿瘤病理， 2005， 硕士

【摘要】 卵巢癌由于其早期诊断困难和其特殊的浸润方式,5年生存率极低。在妇科恶性肿瘤中其死亡率居首位。大约80%卵巢恶性肿瘤是上皮性肿瘤。在卵巢癌的发生发展中有多种基因改变,包括癌基因的激活和抑癌基因的失活。脆性组氨酸三联基因（FHIT）是1996年发现的一个候选抑癌基因,定位于3p14.2,跨越脆性位点FRA3B及家族性肾透明细胞癌易位t（3;8）区。FHIT基因在所有人类组织中均有低水平的表达。而在许多人类肿瘤细胞发现了该基因的高频缺失和/或异常转录,基因的失活最终导致肿瘤细胞缺少正常的抑癌基因蛋白质。 引起基因表达异常的机制主要有两种:即基因机制和表基因机制。表基因改变可通过基因甲基化而发生。甲基化是指DNA的CpG岛中,胞嘧啶被甲基集团修饰,引起基因异常表达,还可引起染色体结构改变。导致基因表达不稳定。 很多组织学正常的组织发现FHIT基因异常转录,如外周血淋巴细胞、骨骼肌和肝脏组织。卵巢癌中FHIT基因结构或表达异常国外已有少量报道:用MSP技术检测到了非小细胞肺癌患者血清中P₁₁、DAP、GSTP₁、MGMT等基因启动子区CPG岛高甲基化状态的存在。FHIT基因甲基化与FHIT蛋白表达缺失显著相关。若能在卵巢癌患者的血清中检测到FHIT基因的甲基化,就可将FHIT基因甲基化作为肿瘤标记物,从而利于卵巢癌早期诊断。 卵巢癌组织中FHIT蛋白缺失或异常表达,而在良性卵巢肿瘤及正常卵巢组织更多还原

【Abstract】 Ovarian cancer represents the most frequent cause of death for gynaecologic malignancies.In fact, after primary surgery,the overall 5-year survival is still very low,mainly because of lack of improvement in early diagnosis and particular aggressiveness of the disease.Nearly 80% of ovarian malignant tumours are of the epithelial type,with multiple genetic changes involved in their genesis and progression,including the activation of proto-oncogenes and inactivation of tumour suppressor genes.The FHIT(Fragile Histidine Triad)gene is a probable tumor suppressor gene,it’s located at 3pl4.2 and encompasses the FRA3B fragile site and the breakpoint of the (3:8)translocation associated with familial renal cell carcinoma .The FHIT gene is expressed at low level in various human tissues.Whereas the high frequency loss and /or aberrant transcripts of FHIT has been reported in various human cancers, inactivation eventually lead to lack of normal anti-oncogene expression in tumor cells. Abnormal structure or expression of fhit gene in ovarian cancer have been reported abroad. Loss or aberrant expression of fhit protein was observed in the ovarian carcinoma but normal expression of FHIT protein wasobserved in benign ovarian tumour and normal ovarian tissue, FHIT protein is important suppressor gene in malignancies,the expression of the FHIT protein is related to histological grade of tumors and prognosis . It is being studied that abnormal expression of FHIT protein in ovarian cancers may be used to diagnose the patients in early stage and evaluate therapeutical effect and direct the clinical treatment.In this project ,the fhit protein is examinated in ovarian benign and malignant tumours.In order to indicate the location,distribution of the FHIT protein in ovarian cancer cells, and the relationship between the FHIT protein expression and the clinicopathological features.Moreover,the role of FHIT protein in the genesis and development of ovarian cancers and the relationships among FHIT protein,the clinicopathological manifestation and the prognosis.In addition,in order to provide the theoretics basis for the early diagnosis ,biological and genetic treatment on ovarian caners. 1.Methods:1.1 Expression of fhit protein was analysed by immunohistochemistry in paraffin embedded 37 ovarian carcinomas, 10 benign adenomas and 5 normal ovarian tissue, and the results were studied in correlation with clinicopathological characteristics of patients.1.2 Statistical treat: All experimental data from expression of FHIT protein and clinicopathological index were analyzed using Fisher’s exact test of probabilities and chi-square test and processed by spss10.0 There was a statistical significance when P<0.05.2.ResuIts:2.1 The FHIT protein located in cytoplasm of the ovarian tissue, benign adenomas and the ovarian cancer cells.2.2 Strongly positive staining was observed in 10 benign adenomas and 5 normal ovarian.2.3 Loss or significantly reduced expression of FHIT protein was observed in 5/37(13.51%) ovarian carcinomas.2.4 The impaired expression of the FHIT protein was significantly related to high malignant potential. Including high histological grade, lymph node metastasis,and the size of residual tumor after operation(p<0.05) 3.ConcIusion:3.1 Loss of FHIT protein characterizes ovarian cancer.3.2 Expression of fhit protein in ovarian carcinomas was lower significantly than benign adenomas .This Indicate that the FHIT protein was significantly related to the genesis and development of ovarian cancers,and may become the mark of biology in state of an illness and early diagnosis in ovarian carcinomas.3.3 The expression of the FHIT protein was significantly related to high histological grade, lymph node metastasis,and the size of residual tumor after operation(p<0.05),Indicating that it is related to the genesis , development and prognosis in ovarian carcinomas.更多还原