BACKGROUND: Expression of estrogen receptor alpha (ERα) is predictive for endocrine therapy response and an important prognostic factor in breast cancer. Overexpression of ERα 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 ERα 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 ERα 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.
BACKGROUND: Expression of estrogen receptor alpha (ERα) is predictive for endocrine therapy response and an important prognostic factor in breast cancer. Overexpression of ERα 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 cancerpatients, 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 ERα 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 ERα 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.
Authors: Lan Cao; Ahmed Basudan; Matthew J Sikora; Amir Bahreini; Nilgun Tasdemir; Kevin M Levine; Rachel C Jankowitz; Priscilla F McAuliffe; David Dabbs; Sue Haupt; Ygal Haupt; Peter C Lucas; Adrian V Lee; Steffi Oesterreich; Jennifer M Atkinson Journal: Cancer Lett Date: 2019-06-20 Impact factor: 8.679
Authors: Aleksandra Markiewicz; Marzena Wełnicka-Jaśkiewicz; Jarosław Skokowski; Janusz Jaśkiewicz; Jolanta Szade; Jacek Jassem; Anna J Zaczek Journal: PLoS One Date: 2013-08-08 Impact factor: 3.240
Authors: George Pentheroudakis; Vassiliki Kotoula; Anastasia G Eleftheraki; Eleftheria Tsolaki; Ralph M Wirtz; Konstantine T Kalogeras; Anna Batistatou; Mattheos Bobos; Meletios A Dimopoulos; Eleni Timotheadou; Helen Gogas; Christos Christodoulou; Kyriaki Papadopoulou; Ioannis Efstratiou; Chrisoula D Scopa; Irene Papaspyrou; Dimitrios Vlachodimitropoulos; Helena Linardou; Epaminontas Samantas; Dimitrios Pectasides; Nicholas Pavlidis; George Fountzilas Journal: PLoS One Date: 2013-07-29 Impact factor: 3.240