title: PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate.
abstract: BACKGROUND
  Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer.
  
  
  OBJECTIVE
  To explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression.
  
  
  METHODS
  We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis.
  
  
  METHODS
  The primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses.
  
  
  CONCLUSIONS
  A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19-2.55; p=0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12-2.28; p=0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis.
  
  
  CONCLUSIONS
  Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted.
  
  
  RESULTS
  PTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nava Rodrigues
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Riisnaes
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Miranda
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Ines
authors.initials: I
authors.lastname: Figueiredo
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Rescigno
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Praful
authors.initials: P
authors.lastname: Ravi
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Carmel
authors.initials: C
authors.lastname: Pezaro
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Aurelius
authors.initials: A
authors.lastname: Omlin
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lorente
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Zafeiris
authors.initials: Z
authors.lastname: Zafeiriou
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Mateo
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Amelia
authors.initials: A
authors.lastname: Altavilla
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Sideris
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Diletta
authors.initials: D
authors.lastname: Bianchini
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Grist
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Khin
authors.initials: K
authors.lastname: Thway
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Raquel
authors.initials: R
authors.lastname: Perez Lopez
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Nina
authors.initials: N
authors.lastname: Tunariu
authors.affiliation: Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Parker
authors.affiliation: Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Dearnaley
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Reid
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK. Electronic address: Johann.de-Bono@icr.ac.uk.
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
mesh_terms: D000069501:Abiraterone Acetate / Q000627:therapeutic use*; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000069501:Abiraterone Acetate
keywords: Abiraterone acetate; Immunohistochemistry; PTEN; Prostate cancer