title: Association between Mutation and Expression ofTP53as a Potential Prognostic Marker of Triple-Negative Breast Cancer.
abstract: OBJECTIVE
  TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role ofTP53status as a prognostic and predictive marker of triple-negative breast cancer (TNBC).
  
  
  METHODS
  We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship betweenTP53alteration and clinical outcomes of TNBC patients.
  
  
  RESULTS
  Seventy-seven of 174 TNBC patients were found to harbor aTP53mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001).TP53mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57, respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patients with aTP53missense mutation (5-year distant recurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with aTP53deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316).
  
  
  CONCLUSIONS
  Association betweenTP53mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Park
authors.affiliation: Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hae Hyun
authors.initials: HH
authors.lastname: Jung
authors.affiliation: Samsung Genome Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eunjin
authors.initials: E
authors.lastname: Lee
authors.affiliation: Cancer of Companion Diagnostics, Innovative Cancer Medicine Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eun Yoon
authors.initials: EY
authors.lastname: Cho
authors.affiliation: Life Science Solutions Group, Thermo Fisher Scientific Corporation, Seoul, Korea.
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Bae
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Se Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.|Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.|Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: AmpliSeq; Immunohistochemistry; Prognosis; Triple-negative breast neoplasms; Tumor Suppressor Protein p53; nCounter mRNA expression assay