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背景与目的:APC和β-caten in基因作为W nt通路上重要的成员,其异常在肿瘤的发生、发展过程中起着重要作用。本研究分析了韧带样型纤维瘤病中APC和-βcaten in基因突变,探讨W nt通路中APC/β-caten in基因异常在肿瘤发生中的作用。方法:采用PCR-DHPLC-Sequence的方法分析韧带样型纤维瘤病中APC和-βcaten in基因的突变,免疫组织化学EnV ision+两步法检测β-caten in、cyc linD1和c-myc蛋白的表达。结果:APC基因发生碱基置换突变,均为体系突变,突变率为26.1%(18/69),突变不产生截短APC蛋白。β-caten in基因发生碱基转换,突变率为18.8%(13/69),导致第3外显子的codon41处苏氨酸磷酸化位点转变为丙氨酸。-βcaten in蛋白异常表达阳性率为47.8%(33/69),在APC、β-caten in基因突变阳性和阴性病例间,其异常表达阳性率没有显著差异。β-caten in异常表达阳性病例的c-myc蛋白阳性率(69.7%,23/33)显著高于阴性病例的c-myc阳性率(22.2%,8/36),两者之间有正相关关系(Pearson’s r=0.477),而cyc linD1的表达没有显示出这种相关性和差异。结论:韧带样型纤维瘤病中APC、β-caten in基因存在体系突变,β-caten in蛋白存在异常表达,可能引起c-myc表达增加。韧带样型纤维瘤病中W nt通路存在异常,可能在肿瘤发生中起重要作用。
BACKGROUND & OBJECTIVE: As an important member of Wnt pathway, APC and β-caten in genes play an important role in tumorigenesis and development. This study analyzed the APC and -βcaten in gene mutations in the ligament-like fibromatosis and explored the role of APC / β-caten in gene abnormalities in tumorigenesis in the Wnt pathway. Methods: The mutations of APC and -βcaten in gene were detected by PCR-DHPLC-Sequence method. The expressions of β-catenin, cyclinD1 and c-myc protein were detected by immunohistochemistry EnV ision + . Results: APC gene mutation occurred in all the bases, both of which were system mutations with a mutation rate of 26.1% (18/69). The mutation did not produce truncated APC protein. The base conversion of β-caten in gene was observed. The mutation rate was 18.8% (13/69), leading to the conversion of the threonine phosphorylation site at codon41 of exon 3 to alanine. The positive rate of abnormal expression ofβ-catenin was 47.8% (33/69). There was no significant difference in the positive rate of abnormal expression between APC and β-catenin gene mutation positive and negative cases. The positive rate of c-myc protein (69.7%, 23/33) in β-catenin-positive cases was significantly higher than that in negative cases (22.2%, 8/36) (Pearson’s r = 0.477), whereas cyclinD1 expression did not show this correlation and difference. CONCLUSIONS: APC and β-catenin genes in the ligament-like fibromatosis are mutated and the expression of β-catenin is abnormal, which may result in the increase of c-myc expression. Wnt pathway is abnormal in ligament-like fibromatosis and may play an important role in tumorigenesis.