EGFR gene amplification in breast cancer

Correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations

Rohit Bhargava, William L. Gerald, Allan R. Li, Qiulu Pan, Priti Lal, Marc Ladanyi, Beiyun Chen

Research output: Contribution to journalArticle

217 Citations (Scopus)

Abstract

The human epidermal growth factor receptor (HER) family of receptor tyrosine kinase has been extensively studied in breast cancer; however, systematic studies of EGFR gene amplification and protein overexpression in breast carcinoma are lacking. We studied EGFR gene amplification by chromogenic in situ hybridization (CISH) and protein expression by immunohistochemistry in 175 breast carcinomas, using tissue microarrays. Tumors with >5 EGFR gene copies per nucleus were interpreted as positive for gene amplification. Protein overexpression was scored according to standardized criteria originally developed for HER-2. EGFR mRNA levels, as measured by Affymetrix U133 Gene Chip microarray hybridization, were available in 63 of these tumors. HER-2 gene amplification by fluorescence in situ hybridization (FISH) and protein overexpression by immunohistochemistry were also studied, EGFR gene amplification (copy number range: 7-18; median: 12) was detected in 11/175 (6%) tumors, and protein overexpression was found in 13/175 (7%) tumors. Of the 11 tumors, 10 (91%) with gene amplification also showed EGFR protein overexpression (2+ or 3+ by immunohistochemistry). The EGFR mRNA level, based on Affymetrix U133 chip hybridization data, was increased relative to other breast cancer samples in three of the five tumors showing gene amplification. Exons 19 and 21 of EGFR, the sites of hotspot mutations in lung adenocarcinomas, were screened in the 11 EGFR-amplified tumors but no mutations were found. Three of these 11 tumors also showed HER-2 overexpression and gene amplification. Approximately 6% of breast carcinomas show EGFR amplification with EGFR protein overexpression and may be candidates for trials of EGFR-targeted antibodies or small inhibitory molecules.

Original languageEnglish (US)
Pages (from-to)1027-1033
Number of pages7
JournalModern Pathology
Volume18
Issue number8
DOIs
StatePublished - Aug 2005
Externally publishedYes

Fingerprint

erbB-1 Genes
Status Epilepticus
Gene Amplification
Epidermal Growth Factor Receptor
Breast Neoplasms
Messenger RNA
Mutation
Neoplasms
Proteins
erbB-2 Genes
Immunohistochemistry
Gene Dosage
Oligonucleotide Array Sequence Analysis
Fluorescence In Situ Hybridization
Protein-Tyrosine Kinases
In Situ Hybridization
Exons
Antibodies

Keywords

  • Breast cancer
  • EGFR
  • Gene amplification
  • mRNA expression
  • Mutation
  • Protein overexpression
  • Tissue microarray

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

EGFR gene amplification in breast cancer : Correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. / Bhargava, Rohit; Gerald, William L.; Li, Allan R.; Pan, Qiulu; Lal, Priti; Ladanyi, Marc; Chen, Beiyun.

In: Modern Pathology, Vol. 18, No. 8, 08.2005, p. 1027-1033.

Research output: Contribution to journalArticle

Bhargava, Rohit ; Gerald, William L. ; Li, Allan R. ; Pan, Qiulu ; Lal, Priti ; Ladanyi, Marc ; Chen, Beiyun. / EGFR gene amplification in breast cancer : Correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. In: Modern Pathology. 2005 ; Vol. 18, No. 8. pp. 1027-1033.
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