PMID- 15920544
OWN - NLM
STAT- MEDLINE
DCOM- 20051005
LR  - 20230210
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 18
IP  - 8
DP  - 2005 Aug
TI  - 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.
PG  - 1027-33
AB  - 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.
FAU - Bhargava, Rohit
AU  - Bhargava R
AD  - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 
      10021, USA.
FAU - Gerald, William L
AU  - Gerald WL
FAU - Li, Allan R
AU  - Li AR
FAU - Pan, Qiulu
AU  - Pan Q
FAU - Lal, Priti
AU  - Lal P
FAU - Ladanyi, Marc
AU  - Ladanyi M
FAU - Chen, Beiyun
AU  - Chen B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adenocarcinoma/genetics/metabolism/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Breast Neoplasms/genetics/metabolism/*pathology
MH  - DNA Mutational Analysis/methods
MH  - ErbB Receptors/*genetics/metabolism
MH  - Female
MH  - Gene Amplification
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization/methods
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/genetics/metabolism/pathology
MH  - Middle Aged
MH  - Mutation
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor, ErbB-2/genetics
MH  - Tissue Array Analysis
EDAT- 2005/05/28 09:00
MHDA- 2005/10/06 09:00
CRDT- 2005/05/28 09:00
PHST- 2005/05/28 09:00 [pubmed]
PHST- 2005/10/06 09:00 [medline]
PHST- 2005/05/28 09:00 [entrez]
AID - S0893-3952(22)04573-2 [pii]
AID - 10.1038/modpathol.3800438 [doi]
PST - ppublish
SO  - Mod Pathol. 2005 Aug;18(8):1027-33. doi: 10.1038/modpathol.3800438.