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


Authors: Bhargava, R.; Lal, P.; Chen, B.
Article Title: HER-2/neu and topoisomerase IIα gene amplification and protein expression in invasive breast carcinomas: Chromogenic in situ hybridization and immunohistochemical analyses
Abstract: We studied HER-2/neu (HER-2) and topoisomerase IIα, (topo2a) amplification (using chromogenic in situ hybridization) and overexpression (immunohislochemical 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 HercepTest 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. © American Society for Clinical Pathology.
Keywords: immunohistochemistry; controlled study; human tissue; protein expression; major clinical study; gene deletion; dna-binding proteins; gene amplification; epidermal growth factor receptor 2; tumor markers, biological; breast neoplasms; in situ hybridization; antigens, neoplasm; breast carcinoma; amplification; staining; tumor cell; receptor, erbb-2; invasive carcinoma; dna topoisomerase (atp hydrolysing); chromosome 17; dna topoisomerases, type ii, eukaryotic; overexpression; her-2/neu; chromogenic in situ hybridization; cish; topoisomerase iiαa
Journal Title: American Journal of Clinical Pathology
Volume: 123
Issue: 6
ISSN: 0002-9173
Publisher: Oxford University Press  
Date Published: 2005-06-01
Start Page: 889
End Page: 895
Language: English
DOI: 10.1309/pcfk-8ytq-pywd-534f
PUBMED: 15899781
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 35" - "Export Date: 24 October 2012" - "CODEN: AJCPA" - "Source: Scopus"
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  1. Beiyun Chen
    49 Chen
  2. Priti Lal
    34 Lal