【作者】 杨晓颖；

【导师】 岳天孚； 张颖；

【作者基本信息】 天津医科大学 ， 妇产科学， 2004， 硕士

【摘要】 目的 建立检测子宫内膜癌组织中FHIT基因第5和第8外显子纯合性缺失的方法，研究子宫内膜癌组织中FHIT基因5、8外显子纯合性缺失及其蛋白表达，以及与子宫内膜癌临床病理参数的关系，探讨FHIT基因外显子5、8纯合性缺失与蛋白表达的关系及其在子宫内膜癌发病机制中的作用。 方法 采用PCR法检测54例子宫内膜癌及22例癌旁正常组织、46例正常增生期子宫内膜的FHIT外显子5、8纯合性缺失情况；采用免疫组化SP法检测上述122例病例FHIT蛋白表达的情况；对FHIT基因外显子5、8纯合性缺失和蛋白表达与子宫内膜癌临床病理参数的关系进行分析。 结果 54例子宫内膜癌中外显子5的纯合性缺失率为20％(9／54)，外显子8的纯合性缺失率为9％(5／54)，有2例外显子5，8均缺失；FHIT外显子5、8纯合性缺失率为26％(14／54)，在癌旁正常组织和正常增生期子宫内膜中未发现外显子5、8纯合性缺失，三组相比有显著性差异(P＜0.05)。子宫内膜癌中FHIT蛋白表达降低和／或缺失率为35％(19／54)，在癌旁正常组织和正常增生期子宫内膜中未发现FHIT蛋白降低和／或缺失，三组相比有显著性差异(P＜0.05)，FHIT基因外显子5、8纯合性缺失和蛋白表达降低和／或缺失有关。FHIT基因外显子5、8纯合性缺失和蛋白表达降低和／或缺失仅见于子宫内膜样癌，在临床少见的浆液性癌和透明细胞癌中均未发现。FHIT基因外显子缺失和蛋白表达改变与年龄、是否绝经、肥胖、高血压、未产等雌激素相关特征及组织分化程度、FIGO分期、肌层浸润、淋巴结转移、宫颈／附件／腹膜浸润无明显关系。 结论 FHIT外显子5、8纯合性缺失是FHIT基因失活的重要方式之一，由于FHIT外显子5、8纯合性缺失导致FHIT蛋白表达降低和／或缺失。FHIT外显子5、8纯合性缺失及FHIT蛋白表达降低和／或缺失可能在子宫内膜癌的发生、发展中起重要作用，但与子宫内膜癌的临床病理参数无明显关系。FHIT外显子5、8纯合性缺失及FHIT蛋白表达降低和／或缺失仅见于子宫内膜样癌，但与子宫内膜样癌相关特征无明显关系。FHIT基因突变可能是通过非激素途天津医科大学硕士研究生学位论文径介导子宫内膜癌的发病机制。更多还原

【Abstract】 Objective To investigate the homozygous deletions of exon5 and exon5 and protein expression of the tumor-suppressor gene FHIT in endometrial carcinomas and its relations with histopathological features.To explore the potential role of FHIT in the development and progress of endometrial carcinomas. Methods The homozygous deletions of exon5 and exon5 of FHIT gene was detected in 54 cancer samples of EC, 22 corresponding contiguous normal tissues and 46 normal endometrias by PCR. The protein expression of FHIT was detected in the three series by immunohistochemistry.Results The homozygous deletions of FHIT exon5,8 was observed in 14 out of 54 rumors, with a HDs rate of 26%. The rate of exon5 is 20%(9/54), the rate of exon5 is 9%(5/54); Both HDs of exon5 and exon5 was observed in 2 tumors. The HDs rate of FHIT gene in endometrial carcinomas (26%) was significantly higher than that in corresponding contiguous normal tissues (0/22)and normal endometrias(0/46) (P<0.05). Abnormal FHIT expression (reduced or absent) was noted in 35%( 19/54) of tumor cases, no corresponding contiguous normal tissues and normal endometrias showed abnormal FHIT expression. The relationship of HDS and expression was statistically significant(P=0.000 < 0.05).The homozygous deletions of FHIT exon5,8 and abnormal FHIT expression only were observed in EEC, not in NEEC, but there was no statistically significant differences in them(P>0.05). There was no relationship between FHIT gene HDS or expression and histopathological features.Conclusions Loss of FHIT function by HDs or other mechanisms is an event in endometrial tumorigenesis. HDs of FHIT exon5,8 may cause abnormal FHIT expression. HDs of FHIT exon5,8 and abnormal FHIT expression only were observed in EEC, but not related to estrogenic risk factors. FHIT gene alerations may contribute in carcinogenesis in EC, especially in EEC, through an5estrogen-independent pathway.更多还原