MED12 protein expression in breast fibroepithelial lesions: correlation with mutation status and oestrogen receptor expression.

Autor:	Tan WJ; Department of Pathology, Singapore General Hospital, Singapore Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Chan JY; Department of Medical Oncology, National Cancer Centre Singapore, Singapore., Thike AA; Department of Pathology, Singapore General Hospital, Singapore., Lim JC; Department of Pathology, Singapore General Hospital, Singapore., Md Nasir ND; Department of Pathology, Singapore General Hospital, Singapore., Tan JS; Department of Pathology, Singapore General Hospital, Singapore., Koh VC; Department of Pathology, Singapore General Hospital, Singapore., Lim WK; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore., Tan J; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore., Ng CC; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore., Rajasegaran V; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore., Nagarajan S; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore., Bay BH; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Teh BT; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore., Tan PH; Department of Pathology, Singapore General Hospital, Singapore Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	Journal of clinical pathology [J Clin Pathol] 2016 Oct; Vol. 69 (10), pp. 858-65. Date of Electronic Publication: 2016 Apr 07.
DOI:	10.1136/jclinpath-2015-203590
Abstrakt:	Aims: Recent reports have identified recurrent MED12 somatic mutations in fibroadenomas and phyllodes tumours. The frequency and type of somatic mutations were noted to be similar to those of uterine leiomyomas. We aimed to investigate protein expression of MED12, correlating it to MED12 mutational status and expression of oestrogen receptors (ER). Methods: Immunohistochemistry was performed on a total of 232 fibroepithelial lesions (100 fibroadenomas, 132 phyllodes tumours) diagnosed at the Department of Pathology, Singapore General Hospital using MED12, ERα and ERβ antibodies. Expressions were evaluated in both stroma and epithelium, and correlated with MED12 mutational status. Results: MED12 mutation was significantly associated with high MED12 protein expression (H-score >150) in the stroma (p=0.029), but not in the epithelium. It was not associated with ERα and ERβ protein expression in both stroma and epithelium. MED12 protein expression was significantly correlated with ERα in epithelial (p=0.007) and ERβ in stromal (p=0.049) components. MED12 was not significantly different between fibroadenomas and phyllodes tumours. Epithelial expression of ERα was significantly higher in fibroadenomas (p<0.001) than in phyllodes tumours. Conversely, both epithelial and stromal expression of ERβ was significantly higher in phyllodes tumours (p<0.001). Conclusions: Positive associations observed between MED12 and ERα, ERβ immunohistochemical expression suggest a biological interplay between the proteins. The lack of significant association of MED12 mutation with ER protein expression indicates a need to further explore the functional impact of MED12 mutations on the ER signalling pathway in breast fibroepithelial lesions. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
Databáze:	MEDLINE
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