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MED12 protein expression in breast fibroepithelial lesions: correlation with mutation status and oestrogen receptor expression
  1. Wai Jin Tan1,2,
  2. Jason Yongsheng Chan3,
  3. Aye Aye Thike1,
  4. Jeffrey Chun Tatt Lim1,
  5. Nur Diyana Md Nasir1,
  6. Jane Sie Yong Tan1,
  7. Valerie Cui Yun Koh1,
  8. Weng Khong Lim4,5,
  9. Jing Tan4,5,
  10. Cedric Chuan Yong Ng4,5,
  11. Vikneswari Rajasegaran4,5,
  12. Sanjanaa Nagarajan4,5,
  13. Boon Huat Bay2,
  14. Bin Tean Teh4,5,
  15. Puay Hoon Tan1,2
  1. 1Department of Pathology, Singapore General Hospital, Singapore
  2. 2Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  3. 3Department of Medical Oncology, National Cancer Centre Singapore, Singapore
  4. 4Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore
  5. 5Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore
  1. Correspondence to Dr Puay Hoon Tan, Department of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 7, Diagnostics Tower, Singapore 169856, Singapore; tan.puay.hoon{at}sgh.com.sg

Abstract

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.

  • BREAST
  • IMMUNOHISTOCHEMISTRY
  • HISTOPATHOLOGY

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