title: Prognostic significance of S100A4-expression and subcellular localization in early-stage breast cancer.
abstract: Prognostic factors are useful in order to identify early-stage breast cancer patients who might benefit from adjuvant treatment. The metastasis-promoting protein S100A4 has previously been associated with poor prognosis in breast cancer patients. The protein is expressed in diverse subcellular compartments, including the cytoplasm, extracellular space, and nucleus. Nuclear expression is an independent predictor of poor outcome in several cancer types, but the significance of subcellular expression has not yet been assessed in breast cancer.
  
  
  
  Nuclear and cytoplasmic expression of S100A4 was assessed by immunohistochemistry in prospectively collected tumor samples from early-stage breast cancer patients using tissue microarrays.
  
  
  
  In patients not receiving adjuvant systemic therapy, nuclear or cytoplasmic expression was found in 44/291 tumors (15%). Expression of either nuclear or cytoplasmic S100A4 was associated with histological grade III, triple-negative subtype, and Ki-67-expression. Patients with S100A4-positive tumors had inferior metastasis-free and overall survival compared to S100A4-negative. When expression was analyzed separately, nuclear S100A4 was a significant predictor of outcome, while cytoplasmic was not. In patients who received adjuvant treatment 23/300 tumors (8%) were S100A4-positive, but no tumors displayed nuclear staining alone. S100A4-expression was strongly associated with histological grade III and triple-negative subtype. Although not significant, metastasis-free and overall survival was numerically reduced in patients with S100A4-positive tumors.
  
  
  
  S100A4-expression was associated with poor outcome in early-stage breast cancer, but the low percentage of positive tumors and the modest survival differences imply that the clinical utility in selection of patients for adjuvant treatment is limited.
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, 0424, Nydalen, Oslo, Norway. eivind.valen.egeland@rr-research.no.
authors.forename: Eivind Valen
authors.identifier: 0000-0002-7273-7277
authors.initials: EV
authors.lastname: Egeland
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, 0424, Nydalen, Oslo, Norway.|Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Boye
authors.affiliation: Department of Pathology, Vestre Viken Health Trust, Drammen, Norway.
authors.forename: Daehoon
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Synnestvedt
authors.affiliation: Department of Pathology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Torill
authors.initials: T
authors.lastname: Sauer
authors.affiliation: Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Borgen
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, 0424, Nydalen, Oslo, Norway. gunhild.mari.malandsmo@rr-research.no.|Department of Pharmacy, University of Tromsø, Tromsø, Norway. gunhild.mari.malandsmo@rr-research.no.
authors.forename: Gunhild M
authors.initials: GM
authors.lastname: Mælandsmo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D042541:Intracellular Space; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D021381:Protein Transport; D000071999:S100 Calcium-Binding Protein A4 / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D000071999:S100 Calcium-Binding Protein A4
keywords: Breast cancer; Nuclear localization; Prognostic marker; S100A4