乳腺癌与癌前病变微卫星DNA杂合性缺失研究

摘要

目的 探讨乳腺单纯性导管增生(UDH)、乳腺不典型导管增生(ADH)和浸润性导管癌(IDC)样本中位于3p、17p和17q的5个微卫星DNA(MS)位点杂合性缺失(LOH)的频率和模式.方法 采用显微分离技术分离病变细胞,聚合酶链反应扩增D3S1029、D3S1300、TP53、D17S579、D17S855目的 DNA片段.结果 (1)UDH组D3S1029、D17S855位点LOH频率分别为9.1%和8.3%;ADH组D3S1029、D3S1300、D17S579、D17S855位点LOH频率分别为25.0%、18.2%、10.0%、16.7%,TP53位点未见LOH;IDC组五个MS位点的LOH频率均大于25%.(2)IDC组TP53和D17S579位点LOH的频率显著高于ADH组(P＜0.05);IDC组5个MS位点LOH的频率显著高于UDH组(P＜0.05);IDC组发生多个位点LOH的频率显著高于ADH和UDH组(P＜0.05).结论 (1)5个MS位点的LOH频繁发生于散发性乳腺癌;(2)部分UDH、ADH发生D3S1029、D3S1300、D17S579、D17S855位点的LOH,是否作为乳腺癌前损伤恶变风险的分子标志,需进一步研究.%Objective To study loss of heterozygosity (LOH ) frequency and pattern of the 5 MSs on 3p,17p,17q in unilateral ductal hyperplasia (UDH ) ,atypical ductal hyperplasia (ADH ) and invasive ductal carcinoma (IDC ) groups .Methods (1) Microdis-sect normal control cells and sick cells from HE stained pathological sections ; (2) Amplify objective DNA fragments of D3S1029、 D3S1300、TP53、D17S579、D17S855 by polymorphism chain reaction (PCR) .Results (1) In UDH group ,the frequencies of LOH at D3S1029 and D17S855 were 9 .1％ and 8 .3％ separately ;In ADH group ,the frequencies of LOH at D3S1029 ,D3S1300 ,D17S579 were 25 Sf/a 48 .2％ ,10 .0％ ,16 .7％ separately ,and there was no LOH at TP53 in this group ;In IDC group ,the frequencies of LOH at 5 MS were all over 25％ . (2 )There were significant differences between ADH and UDH ,ADH and IDC groups ( ρ＜0 .05 ), and significant differences between UDH and IDC ,ADH and IDC groups ( ρ＜0 .05 ) .There were significant difference between UDH and ADH ,UDH and IDC groups ( ρ＜0 .05 ). Conclusion (1) LOH of the 5 MS loci is frequent in sporadic breast cancer . (2 ) Whether the LOHpresented at D3S1029 ,D3S1300 ,D17S579 ,D17S855 loci could be regarded as risk factors of putative precursors of breast cancer needs to be studied further.