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

Research paper by Wai Jin WJ Tan, Jason Yongsheng JY Chan, Aye Aye AA Thike, Jeffrey Chun Tatt JC Lim, Nur Diyana ND Md Nasir, Jane Sie Yong JS Tan, Valerie Cui Yun VC Koh, Weng Khong WK Lim, Jing J Tan, Cedric Chuan Yong CC Ng, Vikneswari V Rajasegaran, Sanjanaa S Nagarajan, Boon Huat BH Bay, Bin Tean BT Teh, Puay Hoon PH Tan

Indexed on: 09 Apr '16Published on: 09 Apr '16Published in: Journal of clinical pathology



Abstract

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).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.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).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.