title: Differential tumor expression of inhibitor of differentiation-1 in prostate cancer patients with extreme clinical phenotypes and prognostic implications.
abstract: BACKGROUND
  In the prostate-specific antigen era, potentially indolent prostate tumors are radically treated, causing overtreatment. Molecular prognostic factors might differentiate indolent from aggressive tumors, allowing avoidance of unnecessary treatment.
  
  
  METHODS
  Fifty-two prostate cancer patients (20 organ-confined and 32 metastatic) were selected. All formalin-fixed and paraffin-embedded primary biopsies and matched metastases of 15 of them were evaluated for tumor and endothelial cell Id1 protein expression. Seventy-nine additional patients with organ-confined prostate cancer were selected for Id1 mRNA in silico analysis.
  
  
  RESULTS
  Among metastatic cancer subjects, 48% of primary tumors and 38% of metastases showed Id1 tumor cell expression, and 79% of primary tumors and 81% of metastases showed endothelial immunoreactivity. In the organ-confined group none of them showed Id1 protein tumor cell expression and 50% displayed endothelial expression. In the metastatic patients group, lower levels of Id1 protein predicted a nonsignificant longer overall survival (13 months vs. 7 months; P = .79). In the in silico analysis, however, lower levels of Id1 mRNA predicted a longer disease-free survival (61 months vs. not-reached; P = .018) and the hazard ratio for progression was 0.451 (P = .022) in favor of patients showing lower levels.
  
  
  CONCLUSIONS
  In our cohort, it seems to be a differential epithelial expression of Id1 protein according to the prognostic features (metastatic/poor prognosis vs. organ-confined/good prognosis). In localized tumors treated with radical prostatectomy, higher Id1 mRNA expression levels might predict a higher hazard ratio for progression and a shorter disease-free survival. Further validation of these results in larger prospective series is warranted.
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain; Division of Oncology, Center for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Ponz-Sarvisé
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain; Division of Oncology, Center for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Castañón
authors.affiliation: Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Panizo-Santos
authors.affiliation: Division of Oncology, Center for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Redrado
authors.affiliation: Division of Oncology, Center for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: López
authors.affiliation: Department of Urology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rosell
authors.affiliation: Biobank of Navarra, Navarrabiomed, Pamplona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gil-Aldea
authors.affiliation: Division of Oncology, Center for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Calvo
authors.affiliation: Division of Oncology, Center for Applied Medical Research (CIMA), Pamplona, Spain.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nguewa
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain; Division of Oncology, Center for Applied Medical Research (CIMA), Pamplona, Spain. Electronic address: igbazo@unav.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gil-Bazo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D018572:Disease-Free Survival; D015870:Gene Expression; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012333:RNA, Messenger
keywords: Differential expression; Id1 mRNA; Immunohistochemistry; Prognosis; Prostate cancer