title: CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer.
abstract: OBJECTIVE
  CD73 is an adenosine-generating ecto-enzyme that suppresses antitumor immunity in mouse models of cancer, including prostate cancer. Although high levels of CD73 are associated with poor prognosis in various types of cancer, the clinical impact of CD73 in prostate cancer remains unclear.
  
  
  METHODS
  We evaluated the prognostic value of CD73 protein expression and CD8(+) cell density in 285 cases of prostate cancer on tissue microarray (TMA). Normal adjacent and tumor tissues were evaluated in duplicates.
  
  
  RESULTS
  Univariate and multivariate analyses revealed that high levels of CD73 in normal adjacent prostate epithelium were significantly associated with shorter biochemical recurrence (BCR)-free survival. Notably, CD73 expression in normal epithelium conferred a negative prognostic value to prostate-infiltrating CD8(+) cells. Surprisingly, high levels of CD73 in the tumor stroma were associated with longer BCR-free survival in univariate analysis. In vitro studies revealed that adenosine signaling inhibited NF-κB activity in human prostate cancer cells via A2B adenosine receptors. Consistent with these results, CD73 expression in the prostate tumor stroma negatively correlated with p65 expression in the nuclei of prostate tumor cells.
  
  
  CONCLUSIONS
  Our study revealed that CD73 is an independent prognostic factor in prostate cancer. Our data support a model in which CD73 expression in the prostate epithelium suppresses immunosurveillance by CD8(+) T cells, whereas CD73 expression in the tumor stroma reduces NF-κB signaling in tumor cells via A2B adenosine receptor signaling. CD73 expression, including in normal adjacent prostate epithelium, can thus effectively discriminate between aggressive and indolent forms of prostate cancer.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, Montréal, Quebec, Canada. Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Leclerc
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, Montréal, Quebec, Canada. Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Charlebois
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, Montréal, Quebec, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Chouinard
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, Montréal, Quebec, Canada. Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Allard
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, Montréal, Quebec, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pommey
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, Montréal, Quebec, Canada.
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, Montréal, Quebec, Canada. Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada. john.stagg@umontreal.ca.
authors.forename: John
authors.initials: J
authors.lastname: Stagg
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology
chemical_list: D016328:NF-kappa B; D015720:5'-Nucleotidase