HER-2/neu and topoisomerase IIα gene amplification and protein expression in invasive breast carcinomas -: Chromogenic in situ hybridization and immunohistochemical analyses

被引:43
作者
Bhargava, R [1 ]
Lal, P [1 ]
Chen, BY [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA
关键词
HER-2/neu; topoisomerase II alpha; chromogenic in situ hybridization; CISH; amplification; overexpression; breast carcinoma;
D O I
10.1309/PCFK8YTQPYWD534F
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:889 / 895
页数:7
相关论文
共 26 条
[1]  
BORG A, 1990, CANCER RES, V50, P4332
[2]   Role of proliferation in HER2 status predicted response to doxorubicin [J].
Campiglio, M ;
Somenzi, G ;
Olgiati, C ;
Beretta, G ;
Balsari, A ;
Zaffaroni, N ;
Valgussa, P ;
Ménard, S .
INTERNATIONAL JOURNAL OF CANCER, 2003, 105 (04) :568-573
[3]  
Coon JS, 2002, CLIN CANCER RES, V8, P1061
[4]   Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to early amplicons [J].
Coquelle, A ;
Pipiras, E ;
Toledo, F ;
Buttin, G ;
Debatisse, M .
CELL, 1997, 89 (02) :215-225
[5]  
Di Leo Angelo, 2003, Clin Breast Cancer, V4, P179
[6]  
GUERIN M, 1988, ONCOGENE RES, V3, P21
[7]  
HECK MMS, 1989, J BIOL CHEM, V264, P15161
[8]  
Holden JA, 1997, ANN CLIN LAB SCI, V27, P402
[9]   HER-2/neu and topoisomerase IIα in breast cancer [J].
Järvinen, TAH ;
Liu, ET .
BREAST CANCER RESEARCH AND TREATMENT, 2003, 78 (03) :299-311
[10]  
Järvinen TAH, 1999, GENE CHROMOSOME CANC, V26, P142