title: Endothelin-1: a predictor of extracapsular extension in clinically localized prostate cancer?
abstract: OBJECTIVE
  To assess the value of endothelin-1 (ET-1) expression in predicting extracapsular extension (ECE) in clinically localized prostate cancer (PCa).
  
  
  METHODS
  ET-1 expression was determined by immunohistochemistry on archival needle biopsies (NBs) from 94 patients (49 pT2 and 45 pT3a) who underwent radical prostatectomy (RP) for clinical T1-T2 PCa. Each sample was analysed independently by two pathologists blinded to the clinical data.
  
  
  RESULTS
  In univariate analysis, high ET-1 expression in NBs, pre-operative prostate-specific antigen (PSA) level >10 ng/ml, percentage of positive biopsy cores and NB Gleason score ≥7 were significantly associated with ECE as determined on subsequent RP. No significant association was found between clinical stage and ECE. In multivariate analysis, there was a significant association with high ET-1 expression in NBs (p = 0.006), pre-operative PSA level >10 ng/ml (p = 0.049), and NB Gleason score ≥7 (p = 0.002). These three pre-operative factors combined provided the best model for predicting ECE with 93.3% sensitivity, 49% specificity, 62.5% positive predictive value, 88.9% negative predictive value. The combination yielded a higher concordance index (0.760 vs 0.720) and offered a higher log partial likelihood than the same model without ET1 (112.8 vs 105.7, p = 0.01).
  
  
  CONCLUSIONS
  ET-1 expression was strongly associated with ECE and, when combined with pre-operative PSA level and Gleason score, improved the predictive accuracy of pre-operative NBs. Its assessment in patients with localized PCa might be useful when making treatment decisions. Further studies with standardisation of immunohistochemical staining and multi-institutional validation are now needed to establish the appropriate use of ET-1 staining in PCa staging and to evaluate inter-observer reproducibility.
authors.affiliation: Department of Urology and Andrology, Laboratoire Pol Bouin, CHU Reims, France. johann.menard@wanadoo.fr
authors.forename: Johann
authors.initials: J
authors.lastname: Menard
authors.forename: Anne
authors.initials: A
authors.lastname: Durlach
authors.forename: Coralie
authors.initials: C
authors.lastname: Barbe
authors.forename: Karine
authors.initials: K
authors.lastname: Joseph
authors.forename: Marianne
authors.initials: M
authors.lastname: Lorenzato
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Azemar
authors.forename: Thomas
authors.initials: T
authors.lastname: Perez
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembault
authors.forename: Frederic
authors.initials: F
authors.lastname: Staerman
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000368:Aged; D001707:Biopsy, Needle; D019332:Endothelin-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D012680:Sensitivity and Specificity
chemical_list: D019332:Endothelin-1