title: Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis.
abstract: BACKGROUND
  Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level.
  
  
  METHODS
  Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression.
  
  
  RESULTS
  SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer.
  
  
  CONCLUSIONS
  The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the plasminogen activator protease cascade warrants further investigation.
authors.affiliation: Department of Pathology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Nuran Bektas
authors.initials: NB
authors.lastname: Serce
authors.forename: Andreas
authors.initials: A
authors.lastname: Boesl
authors.forename: Irina
authors.initials: I
authors.lastname: Klaman
authors.forename: Sonja
authors.initials: S
authors.lastname: von Serényi
authors.forename: Erik
authors.initials: E
authors.lastname: Noetzel
authors.forename: Michael F
authors.initials: MF
authors.lastname: Press
authors.forename: Arno
authors.initials: A
authors.lastname: Dimmler
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Ruth
authors.initials: R
authors.lastname: Knuechel
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Edgar
authors.initials: E
authors.lastname: Dahl
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D016016:Proportional Hazards Models; D016601:RNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D016601:RNA-Binding Proteins; C428129:SERBP1 protein, human