软骨肉瘤WIF-1基因甲基化及Wnt-5a蛋白表达的临床病理意义

Clinicopathological significances of WIF-1 gene methylation and Wnt-5a protein expression in chondrosarcoma

目的研究软骨肉瘤中Wnt抑制因子-1基因(WIF-1)启动子区甲基化状态及Wnt-5a蛋白表达情况,探讨其临床病理意义。方法应用甲基化特异性PCR(MSP)法及免疫组织化学SP法,检测61例软骨肉瘤和作为对照的40例软骨瘤组织中,WIF-1启动子甲基化及Wif-1和Wnt-5a蛋白的表达。结果软骨肉瘤WIF-1基因甲基化阳性率和Wnt-5a蛋白表达阳性率均高于软骨瘤组(P<0.05)。软骨肉瘤中发生浸润转移者Wnt-5a蛋白阳性表达率高于未发生浸润转移者(P<0.05)。软骨肉瘤WIF-1基因甲基化与Wif-1蛋白表达下降及Wnt-5a蛋白过表达相关(KappaWif-1值为0.747,PWif-1<0.001;KappaWnt-5a值为0.468,PWnt-5a<0.05)。结论 WIF-1基因甲基化可能在软骨肉瘤发生的早期起作用,软骨肉瘤Wnt-5a蛋白高表达与肿瘤的侵袭性呈正相关,WIF-1基因甲基化与Wnt-5a蛋白过表达在软骨肉瘤形成中可能存在协同作用。

Objective To study the promoter methylation status of Wnt inhibitory factor-1 gene （ WIF-1 ） and the protein expression of Wnt-5 a in chondrosarcoma and then explore their clinicopathological significances. Methods Methy- lation specific PCR（MSP） and immunohistochemical SP method were used respectively to investigate the methylation of WIF-1 gene and the expressions of Wif-1 protein and Wnt-5a protein in 61 chondrosarcoma samples and 40 matched chondroma samples. Results The methylation of WIF-1 gene and the expression of Wnt-Sa protein obviously increased in chondrosarcoma compared with chondroma（P 〈 0.05）. The expression of Wnt-5a protein was significantly higher in tumors with infiltration and/or metastasis than in that without any invasion and metastasis （ P 〈 0.05 ）. The methylation of WIF-1 gene was related to the decreased expression of Wif-1 protein and the over-expression of Wnt-5a protein （ Kappawif Value 0. 747,Pwifl 〈 0,001 ; Kappawnt_Sa Value 0. 468, Pwnt-sa 〈 0.05 ）. Conclusion WIF-1 gene methylation may play an important role in the early stage of chondrosarcoma formation. The over-expression of Wnt-5a protein is positively related to the invasiveness of chondrosarcoma. Synergistic effects might exist between WIF-1 gene methylation and over-expression of Wnt-5a protein in the oncogenesis of chondrosarcoma.