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Absence of transforming growth factor-β type II receptor is associated with poorer prognosis in HER2-negative breast tumours

2009; Elsevier BV; Volume: 21; Issue: 4 Linguagem: Inglês

10.1093/annonc/mdp518

1569-8041

Carlos Eduardo Paiva, Sandra A. Drigo, Fabíola Encinas Rosa, Francisco Alves Moraes Neto, José Roberto Fígaro Caldeira, Fernando Augusto Soares, Maria Aparecida Custódio Domingues, Sílvia Regina Rogatto,

Pancreatic and Hepatic Oncology Research

BackgroundThe clinical relevance of transforming growth factor-beta (TGF-β)-signalling pathway in breast carcinomas (BCs) remained elusive. This study aimed to evaluate the prognostic value of TGF-β1 and transforming growth factor-beta type II receptor (TGF-βRII) expression levels in tumour cells and their association with the established biomarkers in BC.Patients and methodsIn 324 BC from patients with long-term follow-up, the TGF-β1 and TGF-βRII transcript and protein expression levels were assessed.ResultsTGF-β1 and TGF-βRII down-expression was significantly associated with BC. Negative TGF-β1 and TGF-βRII protein status was associated with the development of distant metastasis (P = 0.003 and P = 0.029, respectively). In multivariate analysis, TGF-β1-positive tumours were associated with increased disease-free survival (DFS) [hazard ratio (HR) = 0.489, P = 0.003]. TGF-βRII 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-β1 and TGF-βRII proteins in breast tumour cells was significantly associated with metastasis development.ConclusionsTo the best of our knowledge, this is the first report indicating the relevance of HER2 status in discriminating TGF-βRII as a prognostic marker for DFS and OS in human BC. These data indicate that TGF-βRII protein analysis in tumour cells could be introduced in clinical practice as additional prognostic biomarker in HER2-negative BC.