title: Proteomics-based identification of alpha1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas.
abstract: BACKGROUND
  The identification of pathological markers of breast cancer for either diagnosis, treatment response or for survival is of critical importance.
  
  
  METHODS
  Serum protein profiling using 2-DE separations coupled to matrix-assisted laser desorption ionization mass spectrometry has been used to explore protein alterations in patients with infiltrating ductal breast carcinomas (IDCA). Sera from 39 breast cancer patients and 40 healthy controls were selected for screening study using 2-DE combined with MS. The protein expression patterns obtained after the depletion of high abundance proteins was determined by coomassie blue G-250 stain after 2-DE electrophoresis.
  
  
  RESULTS
  Six proteins that expressed differentially in the IDCA group were found. The expression levels of four isoforms corresponding to haptoglobin precursor and two isoforms of alpha1-antitrypsin precursor (alpha1-AT) were upregulated in sera from breast cancer patients. There was an increased expression of both proteins in the sera of patients with various tumor stages (I, II, III) in comparison to healthy women. Applying immunohistochemistry, we further validated alpha1-AT immunoreactivity in 51 formalin-fixed paraffin-embedded sections of breast tumors. Enhanced expression of alpha1-AT like activity has been found in IDCA breast tumors, as well as, in different histological types of breast cancer. No significant association has been found with lymph node occurrence, while in high tumor categories a tendency to an increased expression of alpha1-AT has been found, thereby suggesting a possible role of this protein in tumor growth.
  
  
  CONCLUSIONS
  These proteins may constitute new and useful markers of breast cancer that offer a clue to a better understanding of inflammatory pathways and carcinogenesis events linked to breast cancer progression.
authors.affiliation: Laboratoire d'Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, Tunisia.
authors.forename: Bechr
authors.initials: B
authors.lastname: Hamrita
authors.forename: Karim
authors.initials: K
authors.lastname: Chahed
authors.forename: Mounir
authors.initials: M
authors.lastname: Trimeche
authors.forename: Christelle Lemaitre
authors.initials: CL
authors.lastname: Guillier
authors.forename: Philippe
authors.initials: P
authors.lastname: Hammann
authors.forename: Anouar
authors.initials: A
authors.lastname: Chaïeb
authors.forename: Sadok
authors.initials: S
authors.lastname: Korbi
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology*; D044584:Carcinoma, Ductal / Q000097:blood / Q000473:pathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006242:Haptoglobins / Q000032:analysis*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000097:blood; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000515:alpha 1-Antitrypsin / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D006242:Haptoglobins; D020033:Protein Isoforms; D000515:alpha 1-Antitrypsin