title: Nuclear osteopontin-c is a prognostic breast cancer marker.
abstract: BACKGROUND
  Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available.
  
  
  METHODS
  Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues.
  
  
  RESULTS
  We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2.
  
  
  CONCLUSIONS
  The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis.
authors.affiliation: Department of Pathology, Wroclaw Medical University, 50-367 Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Zduniak
authors.affiliation: Department of Pathology, Wroclaw Medical University, 50-367 Wroclaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Ziolkowski
authors.affiliation: Department of Oncology, Örebro University Hospital, SE-70185 Örebro, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Ahlin
authors.affiliation: Department of General and Oncological Surgery, Wroclaw Medical University, 50-367 Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Department of General and Oncological Surgery, Wroclaw Medical University, 50-367 Wroclaw, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Uppsala University, 751 05 Uppsala, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Blomqvist
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Uppsala University, 751 05 Uppsala, Sweden.
authors.forename: M-L
authors.initials: ML
authors.lastname: Fjällskog
authors.affiliation: College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267, USA.
authors.forename: G F
authors.initials: GF
authors.lastname: Weber
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism*; D011044:Poland; D011379:Prognosis; D017741:Survivors; D013548:Sweden
chemical_list: D014408:Biomarkers, Tumor; D053495:Osteopontin