title: Frequency of MED12 mutations in phyllodes tumors: Inverse correlation with histologic grade.
abstract: Phyllodes tumor (PT) is a rare breast biphasic tumor with a potential risk of recurrence and metastasis. In this study, the frequency of MED12 mutations in 176 PTs (49 benign, 49 borderline, and 78 malignant) was determined and the prognostic effect of these mutations in malignant type PT was evaluated. Analysis of MED12 mutations was performed by Sanger sequencing targeting the hotspot mutation region (exon 2) of MED12. Immunohistochemistry was also applied for evaluation of MED12 protein expression on tissue microarray blocks for 133 PTs including 50 benign, 50 borderline, and 33 malignant cases. A notable difference in the frequency of MED12 mutations was found according to histologic grade (71.4% of benign PTs, 51% of borderline PTs, 26.9% of malignant PTs; P < 0.001). MED12 protein expression was not correlated with MED12 mutation status. Patients with malignant PTs that harbored MED12 mutations demonstrated improved disease-free survival (DFS) compared with those without MED12 mutation (P = 0.07). MED12 mutation was a common molecular alteration in PT and the frequency of MED12 mutation decreased with increasing histologic grade. In malignant PT, MED12 exon 2 mutations showed improved DFS but without significance. © 2016 Wiley Periodicals, Inc.
authors: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Nara
authors: N
authors: Yoon
authors: Department of Pathology, Graduate School, Kyung Hee University School, Seoul, Korea.
authors: Go Eun
authors: GE
authors: Bae
authors: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: So Young
authors: SY
authors: Kang
authors: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Mi Sun
authors: MS
authors: Choi
authors: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Hye Won
authors: HW
authors: Hwang
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Seok Won
authors: SW
authors: Kim
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Jeong Eon
authors: JE
authors: Lee
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Seok Jin
authors: SJ
authors: Nam
authors: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Gyungyub
authors: G
authors: Gong
authors: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Hee Jin
authors: HJ
authors: Lee
authors: Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea.
authors: Young Kyung
authors: YK
authors: Bae
authors: Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea.
authors: Ahwon
authors: A
authors: Lee
authors: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Eun Yoon
authors: EY
authors: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D018572:Disease-Free Survival; D005091:Exons / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D056892:Mediator Complex / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D003557:Phyllodes Tumor / Q000235:genetics* / Q000473:pathology
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex