Otro
Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours
Registro en:
Annals of Oncology. Oxford: Oxford Univ Press, v. 21, n. 4, p. 734-740, 2010.
0923-7534
10.1093/annonc/mdp518
WOS:000276045600009
Autor
Paiva, C. E.
Linde, Sandra Aparecida Drigo
Rosa, F. E.
Neto, F. A. Moraes
Caldeira, Jose R. F.
Soares, F. A.
Domingues, Maria Aparecida Custódio
Rogatto, Silvia Regina
Resumen
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-beta and transforming growth factor-beta type II receptor (TGF-beta RII) expression levels in tumour cells and their association with the established biomarkers in BC.Patients and methods: In 324 BC from patients with long-term follow-up, the TGF-beta 1 and TGF-beta RII transcript and protein expression levels were assessed.Results: TGF-beta 1 and TGF-beta RII down-expression was significantly associated with BC. Negative TGF-beta 1 and TGF-beta RII protein status was associated with the development of distant metastasis (P = 0.003 and P = 0.029, respectively). In multivariate analysis, TGF-beta 1-positive tumours were associated with increased disease-free survival (DFS) [hazard ratio (HR) = 0.489, P = 0.003]. TGF-beta RII 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 receptor2 (HER2)-negative patients. Absence of TGF-beta 1 and TGF-beta RII 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-beta RII as a prognostic marker for DFS and OS in human BC. These data indicate that TGF-beta RII protein analysis in tumour cells could be introduced in clinical practice as additional prognostic biomarker in HER2-negative BC. Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)