title: The embryonic Brachyury transcription factor is a novel biomarker of GIST aggressiveness and poor survival.
abstract: BACKGROUND
  The T-box transcription factor Brachyury was recently reported to be upregulated and associated with prognosis in solid tumors. Here, we proposed to evaluate the potential use of Brachyury protein expression as a new prognostic biomarker in gastrointestinal stromal tumors (GIST).
  
  
  METHODS
  Brachyury protein expression was analyzed by immunohistochemistry in a cohort of 63 bona fide GIST patients. Brachyury expression profiles were correlated with patients' clinicopathological features and prognostic impact. Additionally, an in silico analysis was performed using the Oncomine database to assess Brachyury alterations at DNA and mRNA levels in GISTs.
  
  
  RESULTS
  We found that Brachyury was overexpressed in the majority (81.0 %) of primary GISTs. We observed Brachyury staining in the nucleus alone in 4.8 % of cases, 23.8 % depicted only cytoplasm staining, and 52.4 % of cases exhibited both nucleus and cytoplasm immunostaining. The presence of Brachyury was associated with aggressive GIST clinicopathological features. Particularly, Brachyury nuclear (with or without cytoplasm) staining was associated with the presence of metastasis, while cytoplasm sublocalization alone was correlated with poor patient survival.
  
  
  CONCLUSIONS
  Herein, we demonstrate that Brachyury is overexpressed in GISTs and is associated with worse outcome, constituting a novel prognostic biomarker and a putative target for GIST treatment.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Filipe
authors.initials: F
authors.lastname: Pinto
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, CEP 14784 400, Sao Paulo, Brazil.
authors.forename: Nathalia C
authors.initials: NC
authors.lastname: Campanella
authors.affiliation: Department of Pathology, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Lucas F
authors.initials: LF
authors.lastname: Abrahão-Machado
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, CEP 14784 400, Sao Paulo, Brazil.|Department of Pathology, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo-Neto
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, CEP 14784 400, Sao Paulo, Brazil.|Upper Digestive Surgery Department, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Antonio T
authors.initials: AT
authors.lastname: de Oliveira
authors.affiliation: Department of Pathology, Hospital Garcia de Orta, Almada, Portugal.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Brito
authors.affiliation: Regenerative Medicine Program, Department of Medicine and Biomedical Sciences, University of Algarve, Faro, Portugal.
authors.forename: Raquel P
authors.initials: RP
authors.lastname: Andrade
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, CEP 14784 400, Sao Paulo, Brazil.|Department of Endoscopy, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Denise P
authors.initials: DP
authors.lastname: Guimarães
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal. ruireis.hcb@gmail.com.|ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal. ruireis.hcb@gmail.com.|Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, CEP 14784 400, Sao Paulo, Brazil. ruireis.hcb@gmail.com.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000401:mortality* / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040081:Protein Array Analysis; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098908:Brachyury Protein
chemical_list: D014408:Biomarkers, Tumor; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein
keywords: Brachyury; GIST; Metastasis; Poor prognosis