Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16964
Title: LRH-1 expression patterns in breast cancer tissues are associated with tumour aggressiveness
Austin Authors: Pang, Jia-Min B;Molania, Ramyar;Chand, Ashwini;Knower, Kevin;Takano, Elena A;Byrne, David J;Mikeska, Thomas;Millar, Ewan KA;Lee, Cheok Soon;O’Toole, Sandra A;Clyne, Colin;Gorringe, Kylie L;Dobrovic, Alexander ;Fox, Stephen B
Affiliation: Department of Pathology, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
Translational Genomics & Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
Cancer Drug Discovery Laboratory, Hudson Institute of Medical Research, Clayton, Victoria, Australia
School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia
Discipline of Pathology, School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
Cancer Pathology, Bosch Institute, University of Sydney, NSW, Australia
Sydney Medical School, University of Sydney, NSW, Australia
Cancer Genomics Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
Issue Date: 28-Jul-2017
Publication information: Oncotarget 2017; 8(48): 83626-83636
Abstract: The significance and regulation of liver receptor homologue 1 (LRH-1, NR5A2), a tumour-promoting transcription factor in breast cancer cell lines, is unknown in clinical breast cancers. This study aims to determine LRH-1/NR5A2 expression in breast cancers and relationship with DNA methylation and tumour characteristics. In The Cancer Genome Atlas breast cancer cohort NR5A2 expression was positively associated with intragenic CpG island methylation (1.4-fold expression for fully methylated versus not fully methylated, p=0.01) and inversely associated with promoter CpG island methylation (0.6-fold expression for fully methylated versus not fully methylated, p=0.036). LRH-1 immunohistochemistry of 329 invasive carcinomas and ductal carcinoma in situ (DCIS) was performed. Densely punctate/coarsely granular nuclear reactivity was significantly associated with high tumour grade (p<0.005, p=0.033 in invasive carcinomas and DCIS respectively), negative estrogen receptor status (p=0.008, p=0.038 in overall cohort and invasive carcinomas, respectively), negative progesterone receptor status (p=0.003, p=0.013 in overall cohort and invasive carcinomas, respectively), HER2 amplification (overall cohort p=0.034) and non-luminal intrinsic subtype (p=0.018, p=0.038 in overall cohort and invasive carcinomas, respectively). These significant associations of LRH-1 protein expression with tumour phenotype suggest that LRH-1 is an important indicator of tumour biology in breast cancers and may be useful in risk stratification.
URI: http://ahro.austin.org.au/austinjspui/handle/1/16964
DOI: 10.18632/oncotarget.18886
ORCID: 0000-0003-3414-112X
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/29137369
Type: Journal Article
Subjects: DNA methylation
NR5A2
breast carcinoma
estrogen signalling
immunohistochemistry
Appears in Collections:Journal articles

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