Correlation of HER2 overexpression with gene amplification and its relation to chromosome 17 aneuploidy: A 5-year experience with invasive ductal and lobular carcinomas

Aziza Nassar, Andras Khoor, Reshmitha Radhakrishnan, Anu Radhakrishnan, Cynthia Cohen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The HER2 oncogene shows expression or amplification, or both, in approximately 15% to 20% of breast cancers and has been associated with poor prognosis and a response to trastuzumab therapy. HER2 gene status determines the eligibility of breast cancer patients for trastuzumab therapy and a large fraction (41-56%) of these patients respond to targeted therapy. Several studies have related the increased expression of HER2 to an increased copy number of chromosome 17, rather than amplification of the HER2 gene. We compared the results of immunohistochemistry and fluorescence in situ hybridization in both invasive ductal and invasive lobular carcinomas, to determine the frequency of chromosome 17 aneuploidy associated with discordant results. In total, 390 invasive ductal carcinomas and 180 invasive lobular carcinomas diagnosed from January 2000 to December 2005 were included in the study only if results were available for immunohistochemistry (HercepTest; DAKO, Carpinteria, California) and fluorescence in situ hybridization (PathVysion HER2 DNA Probe Kit; Abbott Laboratories, Des Plaines, Illinois). Tumors classified as invasive ductal carcinomas were graded according to the Bloom-Richardson grading system. Correlation between the results of immunohistochemistry and fluorescence in situ hybridization was performed for all categories. Among invasive ductal carcinomas, 29% (115/390) showed chromosome 17 aneuploidy, mostly associated with grade 3/HER2 2+ (45%) or grade 2/HER2 3+ (55%) that were not amplified. Also, 34% (12/35) of invasive lobular carcinomas showed chromosome 17 aneuploidy; approximately one-third of these cases were HER2 2+ (33%) and HER2 3+ (37%) that were not amplified. Discordance between the results of immunohistochemistry and fluorescence in situ hybridization in both ductal and lobular carcinomas is largely associated with chromosome 17 aneuploidy.

Original languageEnglish (US)
Pages (from-to)6254-6261
Number of pages8
JournalInternational Journal of Clinical and Experimental Pathology
Volume7
Issue number9
StatePublished - 2014

Fingerprint

Lobular Carcinoma
Ductal Carcinoma
Chromosomes, Human, Pair 17
Gene Amplification
Aneuploidy
Fluorescence In Situ Hybridization
Immunohistochemistry
erbB-2 Genes
Breast Neoplasms
DNA Probes
Oncogenes
Therapeutics
Neoplasms

Keywords

  • Aneuploidy
  • Ductal carcinoma
  • HER2 genes
  • Human chromosome pair 17
  • Human HER2 protein
  • Lobular carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Correlation of HER2 overexpression with gene amplification and its relation to chromosome 17 aneuploidy : A 5-year experience with invasive ductal and lobular carcinomas. / Nassar, Aziza; Khoor, Andras; Radhakrishnan, Reshmitha; Radhakrishnan, Anu; Cohen, Cynthia.

In: International Journal of Clinical and Experimental Pathology, Vol. 7, No. 9, 2014, p. 6254-6261.

Research output: Contribution to journalArticle

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abstract = "The HER2 oncogene shows expression or amplification, or both, in approximately 15{\%} to 20{\%} of breast cancers and has been associated with poor prognosis and a response to trastuzumab therapy. HER2 gene status determines the eligibility of breast cancer patients for trastuzumab therapy and a large fraction (41-56{\%}) of these patients respond to targeted therapy. Several studies have related the increased expression of HER2 to an increased copy number of chromosome 17, rather than amplification of the HER2 gene. We compared the results of immunohistochemistry and fluorescence in situ hybridization in both invasive ductal and invasive lobular carcinomas, to determine the frequency of chromosome 17 aneuploidy associated with discordant results. In total, 390 invasive ductal carcinomas and 180 invasive lobular carcinomas diagnosed from January 2000 to December 2005 were included in the study only if results were available for immunohistochemistry (HercepTest; DAKO, Carpinteria, California) and fluorescence in situ hybridization (PathVysion HER2 DNA Probe Kit; Abbott Laboratories, Des Plaines, Illinois). Tumors classified as invasive ductal carcinomas were graded according to the Bloom-Richardson grading system. Correlation between the results of immunohistochemistry and fluorescence in situ hybridization was performed for all categories. Among invasive ductal carcinomas, 29{\%} (115/390) showed chromosome 17 aneuploidy, mostly associated with grade 3/HER2 2+ (45{\%}) or grade 2/HER2 3+ (55{\%}) that were not amplified. Also, 34{\%} (12/35) of invasive lobular carcinomas showed chromosome 17 aneuploidy; approximately one-third of these cases were HER2 2+ (33{\%}) and HER2 3+ (37{\%}) that were not amplified. Discordance between the results of immunohistochemistry and fluorescence in situ hybridization in both ductal and lobular carcinomas is largely associated with chromosome 17 aneuploidy.",
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