title: Absence of estrogen receptor alpha (ESR1) gene amplification in a series of breast cancers in Taiwan.
abstract: Immunohistochemical expression of ERα, encoded by the ESR1 (estrogen receptor 1) gene located at 6q25.1, is the most important determinant of responsiveness to endocrine therapy in breast cancer. The prevalence and significance of ESR1 amplification in breast cancer remain controversial. We set out to assess ESR1 status and its relevance in breast cancer in Taiwan. We tested tissue samples from 311 invasive carcinomas in a tissue microarray for ESR1 status by fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH). In order to examine its association with ERα and ESR1 status, HER2 status was determined by FISH. Of the carcinomas, 58.8 % (183/311) was ERα positive. None of the carcinomas showed amplification of ESR1 by either method, whereas 24.1 % (75/311) of the carcinomas harbored HER2 amplification. Of the carcinomas, 9.6 % (26/301) showed ESR1 gain (1.3 ≤ ratio ESR1/chromosome 6 < 2) by FISH and 10 % (24/299) by CISH. FISH and CISH results showed a good correlation (κ-coefficient = 0.786). ESR1 gain by FISH and CISH was significantly associated with high-grade (P = 0.0294 and 0.0417, respectively) but not with ERα expression, HER2 status, or overall survival. ERα positivity was significantly associated with better overall survival (P = 0.039). HER2 amplification was significantly related with poor overall survival (P = 0.002). Our data confirm that in breast cancer, HER2 amplification is a frequent genetic aberration and a negative prognostic factor, and show that ESR1 amplification is not a key genetic abnormality in the tumorigenesis of breast cancer in Taiwan.
authors.affiliation: Department of Pathology, Keelung Chang Gung Memorial Hospital, 222 Maijin Road, Keelung, 204, Taiwan, jimrchen@cgmh.org.tw.
authors.forename: Jim-Ray
authors.initials: JR
authors.lastname: Chen
authors.forename: Tsan-Yu
authors.initials: TY
authors.lastname: Hsieh
authors.forename: Huang-Yang
authors.initials: HY
authors.lastname: Chen
authors.forename: Kun-Yan
authors.initials: KY
authors.lastname: Yeh
authors.forename: Kuo-Su
authors.initials: KS
authors.lastname: Chen
authors.forename: Yi-Che
authors.initials: YC
authors.lastname: ChangChien
authors.forename: Mariann
authors.initials: M
authors.lastname: Pintye
authors.forename: Liang-Che
authors.initials: LC
authors.lastname: Chang
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Hwang
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Chien
authors.forename: Yuan-Chun
authors.initials: YC
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016016:Proportional Hazards Models; D013624:Taiwan; D046888:Tissue Array Analysis
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha
references.citation: J Clin Oncol. 1999 May;17(5):1474-81
references.pmid: 10334533
references.citation: Am J Clin Pathol. 2009 Apr;131(4):490-7
references.pmid: 19289584
references.citation: J Pathol. 2008 Aug;215(4):398-410
references.pmid: 18484683
references.citation: Int J Cancer. 2012 Jun 1;130(11):2629-37
references.pmid: 21702035
references.citation: Nat Genet. 2007 May;39(5):655-60
references.pmid: 17417639
references.citation: J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):529-36
references.pmid: 1562523
references.citation: Nature. 2012 Oct 4;490(7418):61-70
references.pmid: 23000897
references.citation: J Pathol. 2012 May;227(1):8-16
references.pmid: 22170254
references.citation: J Pathol. 2008 Dec;216(4):399-407
references.pmid: 18810758
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1323-33
references.pmid: 19204209
references.citation: Nat Rev Cancer. 2011 Jul 22;11(8):597-608
references.pmid: 21779010
references.citation: Cancer Sci. 2009 Jun;100(6):1012-7
references.pmid: 19320640
references.citation: Endocr Rev. 2013 Feb;34(1):1-32
references.pmid: 22947396
references.citation: J Steroid Biochem Mol Biol. 2014 Jan;139:245-51
references.pmid: 23523517
references.citation: Genome Res. 2010 Sep;20(9):1198-206
references.pmid: 20631050
references.citation: Breast Cancer Res Treat. 2010 Oct;123(3):757-65
references.pmid: 20033484
references.citation: Nat Genet. 2008 Jul;40(7):809; author reply 810-2
references.pmid: 18583967
references.citation: Breast Cancer Res Treat. 2011 Jun;127(2):345-55
references.pmid: 20556506
references.citation: Lancet Oncol. 2011 Nov;12(12):1134-42
references.pmid: 21917518
references.citation: Biochem Biophys Res Commun. 1990 Jan 30;166(2):601-7
references.pmid: 2302226
references.citation: Am J Clin Pathol. 2011 Jan;135(1):157-62
references.pmid: 21173138
references.citation: Histopathology. 2011 Nov;59(5):984-92
references.pmid: 22092410
references.citation: J Clin Pathol. 2010 Mar;63(3):210-9
references.pmid: 20203220
references.citation: J Clin Oncol. 2007 Jan 1;25(1):118-45
references.pmid: 17159189
references.citation: Ann Oncol. 2012 May;23(5):1138-1144
references.pmid: 21986093
references.citation: Nat Genet. 2008 Jul;40(7):809-10; author reply 810-2
references.pmid: 18583966
references.citation: Anal Cell Pathol (Amst). 2010;33(1):13-8
references.pmid: 20966540
references.citation: Lab Invest. 2008 May;88(5):491-503
references.pmid: 18332872
references.citation: Nat Genet. 2008 Jul;40(7):806-7; author reply 810-2
references.pmid: 18583964
references.citation: Oncologist. 2009 Apr;14(4):320-68
references.pmid: 19346299
references.citation: Int J Cancer. 2008 Dec 15;123(12):2970-2
references.pmid: 18816632
references.citation: J Clin Pathol. 2013 Feb;66(2):140-5
references.pmid: 23268322
references.citation: Nat Genet. 2008 Jul;40(7):807-8; author reply 810-2
references.pmid: 18583965