PMID- 20966540
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20211020
IS  - 2210-7185 (Electronic)
IS  - 2210-7177 (Print)
IS  - 2210-7177 (Linking)
VI  - 33
IP  - 1
DP  - 2010
TI  - ESR1 amplification is rare in breast cancer and is associated with high grade and 
      high proliferation: a multiplex ligation-dependent probe amplification study.
PG  - 13-8
LID - 10.3233/ACP-CLO-2010-0527 [doi]
AB  - BACKGROUND: Expression of estrogen receptor alpha (ERalpha) is predictive for 
      endocrine therapy response and an important prognostic factor in breast cancer. 
      Overexpression of ERalpha can be caused by estrogen receptor 1 (ESR1) gene 
      amplification and was originally reported to be a frequent event associated with 
      a significantly longer survival for ER-positive women treated with adjuvant 
      tamoxifen monotherapy, which was however questioned by subsequent studies. 
      METHODS: This study aimed to reanalyze the frequency of ESR1 amplification by 
      multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ 
      hybridisation (FISH), and to assess clinicopathologic correlations. MLPA was 
      performed in a group of 135 breast cancer patients, and gains/amplifications were 
      subjected to FISH. RESULTS: True ESR1 amplification by MLPA was rare (2%) and 
      only 6% more patients showed a modest gain of ESR1. All MLPA-detected ESR1 
      amplifications and nearly all ESR1 gains were also FISH amplified and gained, but 
      not all FISH amplifications/gains were MLPA amplified/gained, leading to an 
      overall concordance of only 60% between both techniques. All 3 MLPA and FISH ESR1 
      amplified cases had high ERalpha expression, but there was no obvious correlation 
      between ESR1 gain and ER status by IHC. ESR1 gains/amplifications were not 
      associated with HER2 gain/amplification, but seemed to be associated with older 
      age. Surprisingly, ESR1 gain/amplification was not associated with low grade as 
      reported previously, but correlated with high grade and high proliferation. 
      Furthermore, ESR1 gain/amplification by MLPA was not associated with nodal status 
      or tumor size (pT status). CONCLUSIONS: ESR1 amplification as detected by MLPA is 
      rare in breast cancer, and seems to be associated with high ERalpha expression, high 
      age, high grade and high proliferation. This study confirms previous studies that 
      showed differences in the ESR1 amplification frequencies detected by different 
      techniques.
FAU - Moelans, Cathy B
AU  - Moelans CB
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht, The 
      Netherlands. cmoelans@umcutrecht.nl
FAU - Monsuur, Hanneke N
AU  - Monsuur HN
FAU - de Pinth, Johannes H
AU  - de Pinth JH
FAU - Radersma, Remco D
AU  - Radersma RD
FAU - de Weger, Roel A
AU  - de Weger RA
FAU - van Diest, Paul J
AU  - van Diest PJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Anal Cell Pathol (Amst)
JT  - Analytical cellular pathology (Amsterdam)
JID - 101541993
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
SB  - IM
RPI - Cell Oncol (Dordr). 2011 Oct;34(5):489-94. PMID: 21541733
MH  - Breast Neoplasms/*genetics/*pathology
MH  - Cell Proliferation
MH  - Estrogen Receptor alpha/*genetics/metabolism
MH  - Female
MH  - *Gene Amplification
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - *Nucleic Acid Amplification Techniques
MH  - Polymerase Chain Reaction
PMC - PMC4605667
EDAT- 2010/10/23 06:00
MHDA- 2011/02/18 06:00
PMCR- 2010/04/26
CRDT- 2010/10/23 06:00
PHST- 2010/10/23 06:00 [entrez]
PHST- 2010/10/23 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
PHST- 2010/04/26 00:00 [pmc-release]
AID - 02L6837051608424 [pii]
AID - 619180 [pii]
AID - 10.3233/ACP-CLO-2010-0527 [doi]
PST - ppublish
SO  - Anal Cell Pathol (Amst). 2010;33(1):13-8. doi: 10.3233/ACP-CLO-2010-0527.