title: RECK is not an independent prognostic marker for breast cancer.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Higher 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.
  
  
  CONCLUSIONS
  Although it continues to serve as an invasion and MMP inhibitor in breast cancer, RECK expression analysis is not useful for prognosis of these patients.
authors.affiliation: 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, São Paulo, 05360-130, SP, Brazil. luciana.gomes@usp.br.
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Gomes
authors.affiliation: Departamento de Ciência da Computação, Instituto de Matemática e Estatística, Universidade de São Paulo, São Paulo, SP, Brazil. fujita@ime.usp.br.
authors.forename: André
authors.initials: A
authors.lastname: Fujita
authors.affiliation: Lawrence Berkeley National Laboratory, Life Science Division, Berkeley, CA, USA. jdmott@lbl.gov.
authors.forename: Joni D
authors.initials: JD
authors.lastname: Mott
authors.affiliation: Departamento de Anatomia Patológica, Hospital A. C. Camargo, Fundação Antônio Prudente, São Paulo, SP, Brazil. fasoares@me.com.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: 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, São Paulo, 05360-130, SP, Brazil. labriola@iq.usp.br.
authors.forename: Leticia
authors.initials: L
authors.lastname: Labriola
authors.affiliation: 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, São Paulo, 05360-130, SP, Brazil. mcsoga@iq.usp.br.
authors.forename: Mari C
authors.initials: MC
authors.lastname: Sogayar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C115460:RECK protein, human; D020780:Matrix Metalloproteinase 9