title: Prognostic implications of securin expression and sub-cellular localization in human breast cancer.
abstract: OBJECTIVE
  Securin belongs to a class of cell cycle regulators that prevent metaphase-to-anaphase transition until sister chromatid separation is complete. Evidence is accumulating that securin has a prognostic impact on a variety of malignancies but, thus far, the role and regulation of securin expression and its sub-cellular localization have not been systematically addressed in breast cancer.
  
  
  METHODS
  In total 470 breast cancer specimens with follow-up data for up to 22 years were included. Immunohistochemical staining and immunofluorescence double-staining were performed for securin and its regulating proteins PTTG1IP, CDC20 and BUBR1. Prognostic associations were evaluated between the expression patterns of these proteins and established prognosticators of invasive breast cancer and patient survival.
  
  
  RESULTS
  We found that a high fraction of securin expressing cancer cells predicted an unfavorable clinical outcome of the breast cancer patients (p < 0.001). Also in multivariate analyses, the fraction of securin expressing cancer cells served as an independent prognosticator of a poor survival (p < 0.0001). We also found that the sub-cellular localization of securin exhibited prognostic power, since cytoplasmic securin expression in the cancer cells appeared to be associated with aggressive breast cancer subtypes and high breast cancer-associated mortality rates (p = 0.003). Through immunofluorescence double-staining, we found that PTTG1IP, CDC20 and BUBR1 exhibited distinct patterns of co-expression with securin, suggesting a regulatory role in the metaphase-to-anaphase transition in human breast cancer cells. We also noted that a subgroup of triple-negative breast carcinomas exhibited deviant expression patterns for the proteins studied.
  
  
  CONCLUSIONS
  Our data indicate that securin expression may serve as a strong and independent prognosticator of breast cancer outcome and that a cytoplasmic localization of the protein may provide additional prognostic information, particularly in the biologically and clinically challenging subgroup of triple-negative breast carcinomas. The sub-cellular localization of securin appears to reflect the expression of PTTG1IP, CDC20 and BUBR1, which may participate in the regulation of securin activity and, ultimately, in the survival of breast cancer patients.
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 20500, Turku, Finland. natalia.gurvits@utu.fi.
authors.forename: N
authors.initials: N
authors.lastname: Gurvits
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 20500, Turku, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Repo
authors.affiliation: Department of Biostatistics, University of Turku, Turku, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Löyttyniemi
authors.affiliation: Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Nykänen
authors.affiliation: Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Anttinen
authors.affiliation: Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Kuopio
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 20500, Turku, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Talvinen
authors.affiliation: Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 20500, Turku, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Kronqvist
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D064249:Securin / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human
keywords: BUBR1; Breast cancer; CDC20; PTTG1IP; Prognosis; Securin