title: MED12 exon 2 mutation as a highly sensitive and specific marker in distinguishing phyllodes tumours from other spindle neoplasms of the breast.
abstract: Spindle neoplasms of the breast (SNB) primarily include metaplastic breast carcinoma (MBC), phyllodes tumour (PT), fibromatosis and primary nonspecific sarcoma (PNS). Mutations in MED12 exon 2 have been reported in PTs. Because spindle tumour components are shared by SNB, we assessed the diagnostic use of MED12 exon 2 mutation in SNB. We investigated MED12 exon 2 mutations in a total of 91 samples of SNB, including 49 PT cases that have been previously analysed. Mutations were identified using direct sequencing. MED12 exon 2 mutation was absent in all cases of MBC, fibromatosis and PNS, in contrast to the 71.4% positivity in PTs. MED12 mutations were identified in four of six previously diagnosed monophasic sarcomatous MCB cases, however, these four cases were revised as malignant PT based on additional bcl-2 staining, albeit very focal. Consistence in the MED12 mutational status between a paired core biopsy and a surgical specimen was observed in all 20 tested PT cases. In conclusion, we demonstrated the restriction of MED12 exon 2 mutation to PTs (73.6%, 39/53) and its absence in other SNB. MED12 exon 2 mutational analysis can be included in the differential diagnosis between PT and other SNB, especially with limited specimen where diagnostic clues are not evident.
authors: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan.
authors: Huang-Chun
authors: HC
authors: Lien
authors: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors: Chiun-Sheng
authors: CS
authors: Huang
authors: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors: Ya-Wen
authors: YW
authors: Yang
authors: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan.
authors: Yung-Ming
authors: YM
authors: Jeng
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D003937:Diagnosis, Differential; D005091:Exons; D005260:Female; D006801:Humans; D056892:Mediator Complex / Q000235:genetics*; D009154:Mutation; D057089:Pathology, Molecular / Q000379:methods*; D003557:Phyllodes Tumor / Q000175:diagnosis* / Q000473:pathology; D017422:Sequence Analysis, DNA
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex
keywords: MED12 exon 2 mutation; metaplastic breast carcinoma; phyllodes tumours