外阴癌和外阴尖锐湿疣FHIT基因杂合性缺失和微卫星不稳定性

目的:探讨脆性组氨酸三联体(FHIT)基因杂合性缺失(LOH)和/或微卫星不稳定性(MSI)与外阴癌发生、发展的相关性。方法:应用聚合酶链反应-单链构象多态性分析(PCR-SSCP)法和DNA序列分析方法,分别对30例外阴癌石蜡切片组织中FHIT基因两个微卫星多态性位点D3S1300和D3S1481进行研究,并以40例外阴尖锐湿疣新鲜组织、20例正常外阴组织作对照。结果:D3S1300位点上,外阴癌、外阴尖锐湿疣、正常外阴组织LOH和/或MSI发生频率分别是50.0%(8/16)、22.5%(9/40)、0%,阳性率外阴癌组高于外阴尖锐湿疣组(P<0.05)。D3S1481位点上,外阴癌未提供信息,外阴尖锐湿疣、正常组织的LOH和/或MSI发生频率分别为20.0%、0%(P<0.05)。40例外阴尖锐湿疣中有15例(37.5%)至少存在一个位点的LOH/MSI。结论:①FHIT基因D3S1300位点在外阴癌中具有较高的LOH和/或MSI,FHIT基因频发异常,FHIT基因LOH和/或MSI与外阴癌的发生、发展有关。②外阴尖锐湿疣可能是外阴鳞癌的前期病变。

Study on loss of heterozygosity and Microsateilite instability of FHIT gene in vulva cancer and vulva condyloma acuminatum.

Objective:To study the LOH/MSI on FHIT gene in vulva cancer and vulva condyloma acuminatum.Methods:PCR-SSCP was used to detect the LOH/MSI in 30 cases of vulva cancer,40 cases of vulva condyloma acuminatum and 20 cases of normal vulva epithelium for amplification with 2 polymorphic microsatellite repeats on FHIT gene(chromosome 3p14).Results:In D3S1300,the LOH/MSI were 50.0%(8/16)in vulva cancer,22.5% in vulva condyloma acuminatum and 0% in normal vulva epithelium.The LOH/MSI in D3S1481 loci could not detected in vulva cancer,20.0% in vulva condyloma acuminatum and 0% in normal vulva epithelium.Conclusion:There are high frequency of LOH/MSI in the D3S1300 and recurrent mutation on FHIT gene.Prompting that:the LOH/MSI on FHIT gene may play an important role in the development and progression of vulva cancer. Vulva condyloma acuminata may be a precancerous stage of vulva cancer.