title: Tissue biomarkers of breast cancer and their association with conventional pathologic features.
abstract: BACKGROUND
  Tissue protein expression profiling has the potential to detect new biomarkers to improve breast cancer (BC) diagnosis, staging, and prognostication. This study aimed to identify tissue proteins that differentiate breast cancer tissue from healthy breast tissue using protein chip mass spectrometry and to examine associations with conventional pathological features.
  
  
  METHODS
  To develop a training model, 82 BC and 82 adjacent unaffected tissue (AT) samples were analysed on cation-exchange protein chips by time-of-flight mass spectrometry. For validation, 89 independent BC and AT sample pairs were analysed.
  
  
  RESULTS
  From the protein peaks that were differentially expressed between BC and AT by univariate analysis, binary logistic regression yielded two peaks that together classified BC and AT with a ROC area under the curve of 0.92. Two proteins, ubiquitin and S100P (in a novel truncated form), were identified by liquid chromatography/tandem mass spectrometry and validated by immunoblotting and reactive-surface protein chip immunocapture. The combined marker panel was positively associated with high histologic grade, larger tumour size, lymphovascular invasion, ER and PR positivity, and HER2 overexpression, suggesting that it may be associated with a HER2-enriched molecular subtype of breast cancer.
  
  
  CONCLUSIONS
  This independently validated protein panel may be valuable in the classification and prognostication of breast cancer patients.
authors.affiliation: Hormones and Cancer Division, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Chung
authors.forename: S
authors.initials: S
authors.lastname: Shibli
authors.forename: K
authors.initials: K
authors.lastname: Moore
authors.forename: E E
authors.initials: EE
authors.lastname: Elder
authors.forename: F M
authors.initials: FM
authors.lastname: Boyle
authors.forename: D J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: R C
authors.initials: RC
authors.lastname: Baxter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D025801:Ubiquitin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; C103003:S100P protein, human; D025801:Ubiquitin