乳腺癌和乳腺增生细胞微卫星DNA杂合性缺失

Loss of heterozygosity of microsatellites in sporadic invasive breast cancer and in breast hyperplasia

目的研究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)位点的杂合性缺失(LOH)的频率和模式。方法采用手工显微切割技术分离HE染色乳腺病理切片病变细胞和正常细胞。聚合酶链反应扩增D3S1029、D3S1300、TP53、D17S579、D17S855目的DNA片段。结果UDH组D3S1029、D17S855位点LOH频率分别为9.1%和8.3%;ADH组D3S1029、D3S1300、D17S579和D17S855位点LOH频率分别为25.0%、18.2%、10.0%和16.7%,TP53位点未见LOH;IDC组5个MS位点的LOH频率均大于25%。UDH组与ADH组、ADH组与IDC组发生一个MS位点LOH频率差异有统计学意义(P<0.05);UDH组与IDC组、ADH组与IDC组在多个MS位点发生LOH频率差异有统计学意义(P<0.05);UDH组与ADH组、UDH组与IDC组总LOH频率差异有统计学意义(P<0.05)。结论5个MS位点的LOH频繁发生于散发性乳腺癌;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 carcinoma （ADH） and invasive ductal carcinoma （IDC） groups. Methods The normal control cells and sick cells from HE stained pathological sections were separated with microdissect lechnique. Objective DNA fragments of D3S1029,D3S1300, TP53, D17S579 and D17S855 were amplified by polymorphism chain reaction （PCR）. Results 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 and D17S855 were 25.0%, 18.2%, 10.0% and 16.7%, respectively. There was no LOH at TP53 in APH group. In IDC group, the frequencies of LOH at 5 MS points were all over 25 %. The differences of the frequencies of LOH between ADH and UDH group or ADH and IDC group at one MS point （P〈0.05） ,between UDH and IDC group or ADH and IDC group at multiple MS points （P〈0. 05）, and total frequency of LOH between UDH and ADH or UDH and IDC group （P〈0.05）, were all significant. Conclusion LOH of the 5 MS loci is present frequently in sporadic breast cancer. Whether the LOH presented at D3S1029, D3S1300, D17S579, D17S855 loci could be regarded as risk factors of putative precursors of breast cancer needs to be sudied further.