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

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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
Externally publishedYes

Fingerprint

Type II DNA Topoisomerase
Gene Amplification
In Situ Hybridization
Neoplasms
Proteins
Chromosomes, Human, Pair 17
Gene Dosage
Breast Carcinoma In Situ
Gene Deletion
Guidelines
Staining and Labeling
Breast Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{e992c9b4e3264d1bb38482b640b955b6,
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.",
keywords = "Amplification, Breast carcinoma, Chromogenic in situ hybridization, CISH, HER-2/neu, Overexpression, Topoisomerase IIαa",
author = "Rohit Bhargava and Priti Lal and Beiyun Chen",
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T1 - HER-2/neu and topoisomerase IIα gene amplification and protein expression in invasive breast carcinomas

T2 - Chromogenic in situ hybridization and immunohistochemical analyses

AU - Bhargava, Rohit

AU - Lal, Priti

AU - Chen, Beiyun

PY - 2005/6

Y1 - 2005/6

N2 - 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.

AB - 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.

KW - Amplification

KW - Breast carcinoma

KW - Chromogenic in situ hybridization

KW - CISH

KW - HER-2/neu

KW - Overexpression

KW - Topoisomerase IIαa

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