RECK is not an independent prognostic marker for breast cancer

BMC Cancer

Research Article

Fernando A. Soares¹  Luciana R. Gomes²  Leticia Labriola²  Mari C. Sogayar²  André Fujita³  Joni D. Mott⁴ 

[1] Departamento de Anatomia Patológica, Hospital A. C. Camargo, Fundação Antônio Prudente, São Paulo, SP, Brazil;Departamento de Bioquímica, Instituto de Química, and NUCEL/NETCEM (Núcleo de Terapia Celular e Molecular), Faculdade de Medicina, Departamento de Clínica Médica, Universidade de São Paulo, Rua Pangaré, 100, 05360-130, São Paulo, SP, Brazil;Departamento de Ciência da Computação, Instituto de Matemática e Estatística, Universidade de São Paulo, São Paulo, SP, Brazil;Lawrence Berkeley National Laboratory, Life Science Division, Berkeley, CA, USA;

关键词: RECK;    Breast cancer;    Immunohistochemistry;    Tissue microarray;    Biomarker;   

DOI  :  10.1186/s12885-015-1666-2

 received in 2014-12-22, accepted in 2015-09-30,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe REversion-inducing Cysteine-rich protein with Kazal motif (RECK) is a well-known inhibitor of matrix metalloproteinases (MMPs) and cellular invasion. Although high expression levels of RECK have already been correlated with a better clinical outcome for several tumor types, its main function, as well as its potential prognostic value for breast cancer patients, remain unclear.MethodsThe RECK expression profile was investigated in a panel of human breast cell lines with distinct aggressiveness potential. RECK functional analysis was undertaken using RNA interference methodology. RECK protein levels were also analyzed in 1040 cases of breast cancer using immunohistochemistry and tissue microarrays (TMAs). The association between RECK expression and different clinico-pathological parameters, as well as the overall (OS) and disease-free (DFS) survival rates, were evaluated.ResultsHigher RECK protein expression levels were detected in more aggressive breast cancer cell lines (T4-2, MDA-MB-231 and Hs578T) than in non-invasive (MCF-7 and T47D) and non-tumorigenic (S1) cell lines. Indeed, silencing RECK in MDA-MB-231 cells resulted in elevated levels of pro-MMP-9 and increased invasion compared with scrambled (control) cells, without any effect on cell proliferation. Surprisingly, by RECK immunoreactivity analysis on TMAs, we found no association between RECK positivity and survival (OS and DFS) in breast cancer patients. Even considering the different tumor subtypes (luminal A, luminal B, Her2 type and basal-like) or lymph node status, RECK remained ineffective for predicting the disease outcome. Moreover, by multivariate Cox regression analysis, we found that RECK has no prognostic impact for OS and DFS, relative to standard clinical variables.ConclusionsAlthough it continues to serve as an invasion and MMP inhibitor in breast cancer, RECK expression analysis is not useful for prognosis of these patients.

【 授权许可】

CC BY   
© Gomes et al. 2015