妊娠滋养细胞疾病c-Ha-ras基因突变及ras p21蛋白表达的研究

C-Ha-ras Gene Mutation and p21 Expression in Gestational Trophoblastic Disease

目的 :探讨c -Ha -ras基因突变及 p21蛋白表达与妊娠滋养细胞疾病 (GTD)发生发展的关系 ,寻找具有特异性的可预测PTD的诊断标记。方法 :采用PCR -SSCP法及SP免疫组化法 ,对90例GTD组织中c -Ha -ras基因第1外显子点突变及其产物 p21表达进行检测 ,以正常足月新鲜胎盘30例为对照。结果 :所有正常胎盘组织ras突变及p21表达均为阴性。ras基因突变在恶性GTD中为36 7 % ,CM将来发展成为PTD的为43 3 % ,均高于CM无PTD发展的16 7 %。恶性GTD,Ⅰ、Ⅱ、Ⅲ级组织分化者点突变率分别为15 4 %、40 %、71 4 % ,各级间差异有显著性 (P<0 01)。不同转归的CM,p21表达不同 ,CM中发展成为PTD者 ,p21表达率为83 3 % ,明显高于未发展成PTD者的43 3 %(P<0 005) ,亦高于恶性GTD的60%(P<0 05)。结论 :GTD的发展演进与ras基因突变及p21表达有关 ,ras突变及p21表达可考虑作为预测PTD的诊断指标之一。GTD由良性到恶性的发展过程中 ,p21表达量存在由低→高→低的内在变化 。

Objective: To study the relationship between the mutation of C-Ha-ras gene and gestational trophoblastic disease (GTD) and to identify diagnostic marker for predicting GTD Methods: The mutation in exon 1 of C-Ha-ras gene and ras p21 expression in 90 cases of GTD and 30 normal placenta were determined by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) and streptavidin peroxidase conjugated method (SP) Results: All of the normal placenta were negative on the mutation in exon 1 of C-Ha-ras gene and p21 expression The mutation rate in exon 1 of C-Ha-ras gene was 36 7%in malignant GTD and 43 3%in complete hydatidiform moles (CM) which culminated in GTD Both of them were 16 7%higher than that of the CM without GTD formation The mutation rate of grade Ⅰ, Ⅱand Ⅲmalignant GTDs were 15 4%, 40%and 71 4%(P<0 01) respectively The positive rate of p21 varied in the different CMs, and was 83 3%in the CM developing to GTD which was significantly higher than the 43 3%of the CM without GTD (P<0 005), and higher than 60%of the malignant GTD ( as well (P<0 05) Conclusion: The development and progression of GTD is associated with the mutation of C-Ha-ras and expression of p21 protein It may be considered as one of the diagnostic marker forecasting GTD undergoing malignant changes