title: Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours.
abstract: BACKGROUND
  The clinical relevance of transforming growth factor-beta (TGF-beta)-signalling pathway in breast carcinomas (BCs) remained elusive. This study aimed to evaluate the prognostic value of TGF-beta1 and transforming growth factor-beta type II receptor (TGF-betaRII) expression levels in tumour cells and their association with the established biomarkers in BC.
  
  
  METHODS
  In 324 BC from patients with long-term follow-up, the TGF-beta1 and TGF-betaRII transcript and protein expression levels were assessed.
  
  
  RESULTS
  TGF-beta1 and TGF-betaRII down-expression was significantly associated with BC. Negative TGF-beta1 and TGF-betaRII protein status was associated with the development of distant metastasis (P = 0.003 and P = 0.029, respectively). In multivariate analysis, TGF-beta1-positive tumours were associated with increased disease-free survival (DFS) [hazard ratio (HR) = 0.489, P = 0.003]. TGF-betaRII positivity was an independent prognostic factor for DFS (HR = 0.439, P = 0.001) and overall survival (OS) (HR = 0.409, P = 0.003) in human epidermal growth factor receptor-2 (HER2)-negative patients. Absence of TGF-beta1 and TGF-betaRII proteins in breast tumour cells was significantly associated with metastasis development.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first report indicating the relevance of HER2 status in discriminating TGF-betaRII as a prognostic marker for DFS and OS in human BC. These data indicate that TGF-betaRII protein analysis in tumour cells could be introduced in clinical practice as additional prognostic biomarker in HER2-negative BC.
authors.affiliation: Oncological and Hemato-oncological Center, São Paulo State University, Botucatu.
authors.forename: C E
authors.initials: CE
authors.lastname: Paiva
authors.affiliation: NeoGene Laboratory, Department of Urology, São Paulo State University, Botucatu and A. C. Camargo Cancer Treatment and Research Center.
authors.forename: S A
authors.initials: SA
authors.lastname: Drigo
authors.affiliation: NeoGene Laboratory, Department of Urology, São Paulo State University, Botucatu and A. C. Camargo Cancer Treatment and Research Center.
authors.forename: F E
authors.initials: FE
authors.lastname: Rosa
authors.affiliation: Departments of Pathology.
authors.forename: F A
authors.initials: FA
authors.lastname: Moraes Neto
authors.affiliation: Departments of Senology, Amaral Carvalho Hospital, Jaú.
authors.forename: J R F
authors.initials: JRF
authors.lastname: Caldeira
authors.affiliation: Department of Pathology, A. C. Camargo Cancer Treatment and Research Center.
authors.forename: F A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Pathology, São Paulo State University, Botucatu, São Paulo, Brazil.
authors.forename: M A C
authors.initials: MAC
authors.lastname: Domingues
authors.affiliation: NeoGene Laboratory, Department of Urology, São Paulo State University, Botucatu and A. C. Camargo Cancer Treatment and Research Center. Electronic address: rogatto@fmb.unesp.br.
authors.forename: S R
authors.initials: SR
authors.lastname: Rogatto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II