title: PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients.
abstract: BACKGROUND
  PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched tumour tissue samples.
  
  
  METHODS
  PTEN gene status in CTCs was evaluated on an enrichment-free platform (Epic Sciences) by fluorescence in situ hybridisation (FISH). PTEN status in archival and fresh tumour tissue was evaluated by FISH and immunohistochemistry.
  
  
  RESULTS
  Peripheral blood was collected from 76 patients. Matched archival and fresh cancer tissue was available for 48 patients. PTEN gene status detected in CTCs was concordant with PTEN status in matched fresh tissues and archival tissue in 32 of 38 patients (84%) and 24 of 39 patients (62%), respectively. CTC counts were prognostic (continuous, P=0.001). PTEN loss in CTCs associated with worse survival in univariate analysis (HR 2.05; 95% CI 1.17-3.62; P=0.01) and with high lactate dehydrogenase (LDH) in metastatic CRPC patients.
  
  
  CONCLUSIONS
  Our results illustrate the potential use of CTCs as a non-invasive, real-time liquid biopsy to determine PTEN gene status. The prognostic and predictive value of PTEN in CTCs warrants investigation in CRPC clinical trials of PI3K/AKT-targeted therapies.
authors.affiliation: Genentech Inc., South San Francisco, CA, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Punnoose
authors.affiliation: The Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, Surrey, UK.|The Institute of Cancer Research, London, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.affiliation: Genentech Inc., South San Francisco, CA, USA.
authors.forename: Edith
authors.initials: E
authors.lastname: Szafer-Glusman
authors.affiliation: Epic Sciences Inc., San Diego, CA, USA.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Tucker
authors.affiliation: Core Diagnostics, Palo Alto, CA, USA.
authors.forename: Sankar
authors.initials: S
authors.lastname: Mohan
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Penelope
authors.initials: P
authors.lastname: Flohr
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Riisnaes
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Miranda
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Ines
authors.initials: I
authors.lastname: Figueiredo
authors.affiliation: The Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, Surrey, UK.
authors.forename: Daniel Nava
authors.initials: DN
authors.lastname: Rodrigues
authors.affiliation: The Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, Surrey, UK.|The Institute of Cancer Research, London, UK.
authors.forename: Aurelius
authors.initials: A
authors.lastname: Omlin
authors.affiliation: The Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, Surrey, UK.|The Institute of Cancer Research, London, UK.
authors.forename: Carmel
authors.initials: C
authors.lastname: Pezaro
authors.affiliation: Genentech Inc., South San Francisco, CA, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Genentech Inc., South San Francisco, CA, USA.
authors.forename: Lukas
authors.initials: L
authors.lastname: Amler
authors.affiliation: Genentech Inc., South San Francisco, CA, USA.
authors.forename: Premal
authors.initials: P
authors.lastname: Patel
authors.affiliation: Genentech Inc., South San Francisco, CA, USA.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Epic Sciences Inc., San Diego, CA, USA.
authors.forename: Natalee
authors.initials: N
authors.lastname: Bales
authors.affiliation: Epic Sciences Inc., San Diego, CA, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Werner
authors.affiliation: Epic Sciences Inc., San Diego, CA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Louw
authors.affiliation: Core Diagnostics, Palo Alto, CA, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Pandita
authors.affiliation: Epic Sciences Inc., San Diego, CA, USA.
authors.forename: Dena
authors.initials: D
authors.lastname: Marrinucci
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
mesh_terms: D000368:Aged; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D007770:L-Lactate Dehydrogenase; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human