散发性乳腺癌和乳腺增生细胞中多个微卫星位点杂合性缺失的研究

Study on loss of heterozygosity of multiple microsatellites in sporadic breast cancer and breast hyperplasia cells

目的检测乳腺典型性(导管)上皮增生(UDH)、乳腺非典型性(导管)上皮增生(ADH)和浸润性导管癌(IDC)细胞中3p、9p、17p、17q上10个微卫星DNA(MS)位点的杂合性缺失(LOH)频率和模式,探讨乳腺癌发生发展过程中LOH的变化规律。方法随机选取28例UDH患者,29例ADH患者和35例IDC患者的病理样本,采用PCR—变性聚丙烯酰胺凝胶电泳—银染法进行LOH分析。结果 1D3S1447、D3S1029、D17S855 3个位点在UDH、ADH、IDC均有一定频率的LOH发生,且有逐渐增高的趋势;2TP53只在IDC中发生LOH;3D3S1612位点的LOH在淋巴结转移阳性组(63%)高于淋巴结转移阴性组(19%)(P<0.05)。结论 1D3S1447、D3S1029、D17S855 3个位点的LOH组合可能是乳腺癌发生的早期分子改变模式;2TP53的LOH可能可作为分析乳腺癌浸润能力、预测复发及预后判断的独立指标;3D3S1612的LOH频率在预测乳腺癌淋巴转移风险上有一定价值。

Objective To detect loss of heterozygosity（LOH） frequency and pattern of 10 microsatellite （MSs） located in 3p, 9p, 17p, 17q in usual ductal hyperplasia（UDH）, atypical ductal hyperplasia（ADH） and invasive ductal carcinoma （IDC） cells, and to explore the variation nile of LOH in the development of breast cancer. Methods The pathological samples were randomly collected from 28 cases of UDH, 29 cases of ADH and 35 cases of IDC to analyze the LOH by PCR - denaturing poly- acrylamide gel electrophoresis -silver staining method. Results. The microsatellite sites （D3S1447, D3S1029 arid D17S855） in UDH, ADH and IDC had a certain frequency LOH, showing a gradually increasing trend from UDH to IDC. The LOH of TP53 was only found in IDC. LOH positive rate of D3S612 in lymph node metastasis group（63% ） was significantly higher than that in non - lymph node metastasis group （ 19% ） in IDC group （P 〈 0.05）. Conclusion LOH in D3S1447, D3S1029 and D17S855 of all the there group cases may be an early molecular change in the development of breast cancer. The LOH of TP53 may be an independent indicator to analyze the invasive ability of breast cancer, predict recurrence and prognosis of breast cancer. The frequency of LOH in D3S1612 has certain value in predicting the risk of lymph node metastasis in breast cancer.