title: Gene expression of PMP22 is an independent prognostic factor for disease-free and overall survival in breast cancer patients.
abstract: BACKGROUND
  Gene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer.
  
  
  METHODS
  In a retrospective multicenter study, gene expression of PMP22 and the EMPs was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data.
  
  
  RESULTS
  In univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median PMP22 gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower PMP22 expression. They also have a 1.77 times higher risk to relapse than those with lower PMP22 expression. The proportion of explained variation in overall survival due to PMP22 gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating PMP22 into the prediction model.
  
  
  CONCLUSIONS
  PMP22 gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis.
authors.affiliation: Department of Obstetrics and Gynaecology, Medical University of Vienna, EBO 5Q, AKH, Währinger Gürtel 18-20, Vienna 1090, Austria. dan.cacsire-castillo@meduniwien.ac.at
authors.forename: Dan
authors.initials: D
authors.lastname: Tong
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
authors.forename: Andrea
authors.initials: A
authors.lastname: Wolf
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Nicole
authors.initials: N
authors.lastname: Concin
authors.forename: Gerda
authors.initials: G
authors.lastname: Hofstetter
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schiebel
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
mesh_terms: D001317:Austria; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D015203:Reproducibility of Results; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D009185:Myelin Proteins; C073687:PMP22 protein, human; D011960:Receptors, Estrogen