子宫内膜样腺癌发生过程中β-catenin蛋白异常表达和基因突变的检测

目的:检测子宫内膜良性增生、子宫内膜上皮内瘤变(EIN)和子宫内膜样腺癌组织中β-catenin蛋白表达和第3外显子基因突变情况,探讨在子宫内膜样腺癌发生过程中β-catenin蛋白异常表达和基因突变的关系。方法:采用免疫组织化学(SP法)和DNA直接测序方法,对10例增殖期子宫内膜、59例良性子宫内膜增生、24例EIN及24例子宫内膜样腺癌组织中β-catenin蛋白表达和第3外显子基因突变进行检测。结果:①10例增殖期子宫内膜β-catenin蛋白均显示正常(膜)表达,无异常表达病例。59例良性子宫内膜增生中53例(89.8%)呈正常(膜)表达,仅6例(10.2%)呈异常表达。24例EIN病变中正常表达及异常表达病例各占12例(50.0%)。在24例子宫内膜样腺癌中,β-catenin蛋白正常表达者8例,占33.3%;异常表达者16例,高达66.7%。在β-catenin蛋白异常表达病例中均以膜/浆表达者为主。EIN和子宫内膜样腺癌中β-catenin蛋白异常表达率(50.0%,66.7%)均明显高于良性子宫内膜增生(10.2%)(P<0.01),但二者间的异常表达率则无显著性差异(P>0.05)。②PCR扩增及测序结果显示,良性子宫内膜增生、EIN及子宫内膜样腺癌病例中均未发现β-catenin基因第3外显子突变。结论:①β-catenin蛋白的异常表达可能是一种区别良性子宫内膜增生和EIN或子宫内膜样腺癌的有用免疫标记物。②β-catenin基因第3外显子突变可能不是导致子宫内膜样腺癌癌变和β-catenin蛋白异常表达的主要原因。

Detection of Beta-Catenin Protein Expression and Gene Mutation in Tumorigenesis of Endometrioid Adenocarcinoma

Objective:To detect the protein expression and the exon 3 mutation of β-catenin in benign hyperplasia,endometrial intraepithelial neoplasia (EIN),and endometrioid adenocarcinoma,and to investigate the relationship between abnormal expression and exon 3 mutation of β-catenin in carcinogenesis of endometrioid adenocarcinoma. Methods:A total of 117 endometrial samples (10 proliferative endometrium,59 benign hyperplasia,24 EIN,and 24 endometrioid adenocarcinoma) were involved in this study. Expression of β-catenin protein was detected by immunohistochemistry. DNA sequence alterations of exon 3 of β-catenin gene were investigated by polymerase chain reaction (PCR) and direct sequencing. Results:① Normal (membranous) expression of β-catenin presents in all the 10 cases of proliferative endometrium. While 6 of 59 benign hyperplasia cases (10.2%) showed abnormal (marked membranous/cytoplasmic and/or nuclear or negative) expression of β-catenin. Abnormal expression rate of β-catenin was 50.0% in 24 cases of EIN,and 66.7% in 24 cases of endometrioid adenocarcinoma respectively. Membranous/cytoplasmic expression of β-catenin was a predominant pattern for abnormal expressions in EIN and endometrioid adenocarcinoma. ② PCR and direct sequencing failed to reveal any exon 3 mutation of β-catenin gene in 117 endometrial specimens (particularly in benign hyperplasia,EIN,and endometrioid adenocarcinoma). Conclusion:①abnormal expression of β-catenin may be a useful marker in distinguishing benign hyperplasia from EIN and endometrioid adenocarcinoma. ②The exon 3 mutation of β-catenin gene may not be an important cause,which result in abnormal expression of β-catenin and tumorigenesis of endometrioid adenocarcinoma.