乳腺浸润性导管癌TOP2A基因状态与HER2及临床病理特征的关系

目的: 检测乳腺浸润性导管癌拓扑异构酶Ⅱα(topoisomerase Ⅱ alpha, TOP2A)基因状态，探讨其与人类表皮生长因子受体2(human epidermal growth factor receptor 2, HER2)基因状态、HER2蛋白表达及临床病理特征之间的相关性。方法: 筛选乳腺浸润性导管癌患者371例，通过荧光原位杂交法(FISH)检测癌组织TOP2A基因状态，同时用双色银染原位杂交法(DISH)检测HER2基因扩增情况，免疫组织化学法(IHC)检测HER2蛋白表达，分析其相关性。结果： 371例患者中TOP2A基因扩增64例，基因缺失12例，异常率20.49%(76/371)；HER2基因扩增122例(32.88%)。TOP2A基因扩增中有53例HER2基因扩增，11例HER2基因无扩增；TOP2A基因缺失中有9例HER2基因扩增，3例HER2基因无扩增；TOP2A基因无扩增或缺失中有60例HER2基因扩增，235例HER2基因无扩增；HER2蛋白表达为0～1+，2+，3+对应的TOP2A基因扩增率分别为4.69%，23.44%，71.88%；HER2表达为3+时TOP2A基因缺失率为66.67%(8/12)。TOP2A基因状态与患者年龄、性别、部位及有无淋巴结转移无明显相关(P>0.05)，与组织分级、肿瘤直径相关(P<0.05)。 结论： TOP2A基因状态与HER2基因异常具有相关性，TOP2A基因扩增随HER2蛋白表达增强而增高；肿瘤直径为2～5 cm，组织分级高的浸润性乳腺癌TOP2A基因异常率高。

Relationship between the status of TOP2A,HER2 gene and clinicopathological characteristics in breast invasive ductal carcinoma

Objective: To detect the topoisomerase Ⅱ alpha(TOP2A) gene in breast invasive ductal carcinoma and explore its association with the status and expression of human epidermal growth factor receptor 2(HER2) gene, as well as the clinicopathological characteristics. Methods: The status of TOP2A gene was detected by fluorescence in situ hybridization(FISH), the amplification of HER2 gene was detected by dual color silver enhanced in situ hybridization(DISH) and the expression of HER2 gene by immunohistochemistry among 371 patients with breast invasive ductal carcinoma. Results: In 371 patients with breast invasive ductal carcinoma, 64 cases(17.25%) of TOP2A amplification, 12 cases(3.24%) of TOP2A deletion and 122 cases(32.88%) of HER2 amplification were found, with the abnormality rate 20.49%(76/371) of TOP2A. In TOP2A amplification, 53 cases of HER2 amplification and 11 cases of non amplification were found.In TOP2A deletion, 9 cases of HER2 amplification and 3 cases of non amplification were found. In TOP2A without amplification or deletion, 60 cases of HER2 amplification and 235 cases of non amplification were found. The expression of HER2 was 0～1+, 2+, 3+ and the corresponding amplification rate of TOP2A gene was 4.69%, 23.44%, 71.88%, respectively. The deletion rate of TOP2A was 66.67%(8/12) at HER2 expression 3+. The status of TOP2A had no statistical association with age, gender, cancer site and lymphatic metastasis(P>0.05), while it was statistically correlated with histological classification and tumor diameter(P<0.05). Conclusion: TOP2A gene was correlated with the abnormality of HER2 gene, and the amplification of TOP2A increased with the increasing expression of HER2 gene. The abnormal rate of TOP2A in invasive breast cancer was relatively high among the patients with tumor diameter of2～5 cm and higher histological classification.