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

Rohit Bhargava, Priti Lal, Beiyun Chen

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)889-895
Number of pages7
JournalAmerican journal of clinical pathology
Volume123
Issue number6
DOIs
StatePublished - Jun 2005

Keywords

  • Amplification
  • Breast carcinoma
  • CISH
  • Chromogenic in situ hybridization
  • HER-2/neu
  • Overexpression
  • Topoisomerase IIαa

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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