HER-2/neu and topoisomerase IIα gene amplification and protein expression in invasive breast carcinomas -: Chromogenic in situ hybridization and immunohistochemical analyses
HER-2/neu and topoisomerase IIα gene amplification and protein expression in invasive breast carcinomas -: Chromogenic in situ hybridization and immunohistochemical analyses
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DOI：
10.1309/pcfk8ytqpywd534f
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发表时间：
2005-06-01
影响因子：
3.5
通讯作者：
Chen, BY
中科院分区：
文献类型：
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作者：
Bhargava, R;Lal, P;Chen, BY
我们对113例浸润性乳腺癌组织中HER-2/neu(HER-2)和拓扑异构酶Ha(Topo2a)的扩增(发色原位杂交)和过表达(免疫组织化学分析)进行了研究。基因拷贝数/17号染色体拷贝数之比为2.0或更高表示扩增。Topo2a/17号染色体比值小于0.8表示基因缺失。根据标准的Hercep试验指南(达科、卡平特里亚、加利福尼亚州)对HER-2过度表达进行评分。当发现超过5%的肿瘤细胞有核染色时，Topo2a过表达。在113例肿瘤中，104例成功进行了HER-2和topo2a扩增分析。在104例中，表现为HER-2扩增，其中25例(39%)同时表现为topo2a扩增。40例肿瘤均未见扩增。在HER-2扩增的肿瘤中有7例(11%)有topo2a缺失，在40例未扩增的肿瘤中有2例(5%)有topo2a的缺失。在25例topo2a扩增的肿瘤中，18例(72%)过表达topo2a。在79例无topo2a扩增的肿瘤中，仅有3例(4%)topo2a过表达。Topo2a的扩增与HER-2的扩增有关，反之亦然。Topo2a扩增导致72%的肿瘤蛋白过表达，但在没有基因扩增的情况下，Topo2a过表达很少发生。Topo2a和HER-2状态的确定可能具有治疗和预后意义。
We studied HER-2/neu (HER-2) and topoisomerase Ha (topo2a) amplification (using chromogenic in situ hybridization) and overexpression (immunohistochemical analysis) in 113 invasive breast carcinomas. A gene copy number/chromosome 17 copy number ratio of 2.0 or higher indicated amplification. A topo2a/chromosome 17 ratio of less than 0.8 indicated gene deletion. HER-2 overexpression was scored according to standard Hercep Test guidelines (DAKO, Carpinteria, CA). Overexpression of topo2a was identified when nuclear staining was found in more than 5% of tumor cells. Of 113 tumors, 104 were analyzed successfully for HER-2 and topo2a amplification. Of the 104, 64 showed HER-2 amplification; 25 of these (39%) also showed topo2a amplification. No amplification was found in 40 tumors. Deletion of topo2a was seen in 7 (11%) of 64 HER-2-amplified tumors and 2 (5%) of 40 nonamplified tumors. Of 25 tumors with topo2a amplification, 18 (72%) overexpressed topo2a. Only 3 (4%) of 79 tumors without topo2a amplification overexpressed topo2a. Amplification of topo2a is associated with HER-2 amplification but not vice versa. Amplification of topo2a resulted in protein overexpression in 72% of tumors, but topo2a overexpression rarely occurred without gene amplification. Identification of topo2a and HER-2 status might have therapeutic and prognostic implications.