乳腺癌组织TOP2A和HER2/neu扩增与临床病理因素相关性研究

目的 拓扑异构酶Ⅱ(typeⅡtopoisomerase,TOP2A) DNA是常见的化疗疗效预测因子,HER2是与乳腺癌相关的重要的原癌基因之一.本研究探讨乳腺癌组织中人类表皮生长因子受体HER2/neu和TopoⅡ之间的关系,及其与临床病理因素之间的相关性.方法 收集广西医科大学附属肿瘤医院2010-02-01-2012-09-30手术治疗的96例乳腺浸润性导管癌标本,实时定量聚合酶链式反应(real time polymerase chainreaction,RQ-PCR)检测和评估基因扩增水平,免疫组织化学(immunohistochemistry,IHC)微阵列(n=76)检查基因扩增和蛋白质表达水平之间是否存在相互关系.结果 根据RQ-PCR或IHC微阵列取得的HER2/neu基因状态,TOP2A基因的扩增水平差异无统计学意义,P值分别为0.481和0.935.在HER2/neu(-)基因型患者中,29.1％(14/48)的患者显示出TOP2A基因水平高于第三四分位值,然而22.9％(11/48)的HER2/neu(+)基因型患者的数值处于第一四分位值(log TOP2A＜0.62),因此表明存在低水平的扩增.采用IHC以及荧光原位杂交(fluorescence in situ hybridization,FISH)方法确定具有HER2/neu-基因型的60例患者中,22.9％(11/48)的患者在IHC微阵列上被归类为TOP2A(+)基因型患者.同时,采用IHC以及FISH法将患者视为HER2/neu(+)基因型患者的14例患者中,大多数患者(n=10)被归类为TOP2A(+)基因型患者.结论 乳腺癌组织中TOP2A基因的扩增并不局限于带有HER2/neu(+)基因型的患者,并且很大比例的HER2/neu(-)基因型患者表现出具有高水平的TOP2A基因.

Topoisomerase amplification and its correlation with HER2/neu in breast cancer patients

OBJECTIVE TOP2A DNA is a common predictor of chemotherapy,and HER2 is the most important one of the original cancer gene associated with breast cancer.This study was to explore the relationship and the clinico pathologic factors of human epidermal growth factor receptor HER2/neu and topoisomerase Ⅱ (Topo Ⅱ relationship) in breast cancer.METHODS Ninty-six cases of surgical treated invasive ductal breast cancer were collectied in Guangxi Medical University Cancer Hospital from February 1,2010 to September 30,2012.Real-Time PCR was used to test the gene amplification.Immunohistochemistry micro-matrix (n=76)was used to test if there was correlation between gene amplification and protein expression level.RESULTS There was no significant correlation for TOP2A gene amplification based on RQ-PCR and IHC micro-Matrix.In HER2/neu negative genotype patients,29.1％ (14/48) patients showed the TOP2A gene level were higher than the third quartile while 22.9％ (11/48) HER2/neu positive genotype patients had first quartile(log TOP2A＜0.62),suggesting low amplification level.Within the 60 HER2/neu positive patients confirmed by IHC and FISH methods,22.9％ of them were classified into the TOP2A(+) genotype.In the mean time,14 HER2/neu positive patients defined by IHC and FISH,most of them (n=10) were classified into the TOP2A+ genotype.CONCLUSIONS TOP2A gene amplification was not limited in HER2/neu positive genotype in breast cancer patients.Large proportion of HER2/neu negative genotype patients also shows high level of TOP2A gene.