title: MED12 protein expression in breast fibroepithelial lesions: correlation with mutation status and oestrogen receptor expression.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Wai Jin
authors.initials: WJ
authors.lastname: Tan
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Jason Yongsheng
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Jeffrey Chun Tatt
authors.initials: JC
authors.lastname: Lim
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Nur Diyana
authors.initials: ND
authors.lastname: Md Nasir
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Jane Sie Yong
authors.initials: JS
authors.lastname: Tan
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Valerie Cui Yun
authors.initials: VC
authors.lastname: Koh
authors.affiliation: 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.
authors.forename: Weng Khong
authors.initials: WK
authors.lastname: Lim
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Cedric Chuan Yong
authors.initials: CC
authors.lastname: Ng
authors.affiliation: 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.
authors.forename: Vikneswari
authors.initials: V
authors.lastname: Rajasegaran
authors.affiliation: 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.
authors.forename: Sanjanaa
authors.initials: S
authors.lastname: Nagarajan
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Boon Huat
authors.initials: BH
authors.lastname: Bay
authors.affiliation: 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.
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D018226:Fibroadenoma / Q000175:diagnosis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D056892:Mediator Complex / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D003557:Phyllodes Tumor / Q000175:diagnosis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D012846:Singapore; D055815:Young Adult
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; C460107:MED12 protein, human; D056892:Mediator Complex; D011960:Receptors, Estrogen
keywords: BREAST; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY