title: The Initial Detection and Partial Characterization of Circulating Tumor Cells in Neuroendocrine Prostate Cancer.
abstract: OBJECTIVE
  The transition of prostate adenocarcinoma to a predominantly androgen receptor (AR) signaling independent phenotype can occur in the later stages of the disease and is associated with low AR expression +/- the development of small-cell or neuroendocrine tumor characteristics. As metastatic tumor biopsies are not always feasible and are difficult to repeat, we sought to evaluate noninvasive methods to identify patients transitioning toward a neuroendocrine phenotype (NEPC).
  
  
  METHODS
  We prospectively studied a metastatic tumor biopsy, serum biomarkers, and circulating tumor cells (CTC, Epic Sciences) from patients with castration-resistant prostate cancer (CRPC) including those with pure or mixed NEPC histology present on biopsy. CTCs labeled with the patient's clinical status were used to learn features that discriminate NEPC patients, which was then applied to an independent cohort.
  
  
  RESULTS
  Twenty-seven patients with CRPC including 12 NEPC and 5 with atypical clinical features suggestive of NEPC transition were studied. CTCs from NEPC patients demonstrated frequent clusters, low or absent AR expression, lower cytokeratin expression, and smaller morphology relative to typical CRPC. A multivariate analysis of protein and morphologic variables enabled distinguishing CTCs of NEPC from CRPC. This CTC classifier was applied to an independent prospective cohort of 159 metastatic CRPC patients and identified in 17/159 (10.7%) of cases, enriched in patients with high CTC burden (P < 0.01) and visceral metastases (P = 0.04).
  
  
  CONCLUSIONS
  CTCs from patients with NEPC have unique morphologic characteristics, which were also identified in a subset of CRPC patients with aggressive clinical features potentially undergoing NEPC transition.
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York. Institute for Precision Medicine, New York Presbyterian-Weill Cornell Medicine, New York, New York. hip9004@med.cornell.edu.
authors.forename: Himisha
authors.initials: H
authors.lastname: Beltran
authors.affiliation: Epic Sciences, San Diego, California.
authors.forename: Adam
authors.initials: A
authors.lastname: Jendrisak
authors.affiliation: Epic Sciences, San Diego, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Landers
authors.affiliation: Institute for Precision Medicine, New York Presbyterian-Weill Cornell Medicine, New York, New York. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.affiliation: Institute for Precision Medicine, New York Presbyterian-Weill Cornell Medicine, New York, New York.
authors.forename: Myriam
authors.initials: M
authors.lastname: Kossai
authors.affiliation: Epic Sciences, San Diego, California.
authors.forename: Jessica
authors.initials: J
authors.lastname: Louw
authors.affiliation: Epic Sciences, San Diego, California.
authors.forename: Rachel
authors.initials: R
authors.lastname: Krupa
authors.affiliation: Epic Sciences, San Diego, California.
authors.forename: Ryon P
authors.initials: RP
authors.lastname: Graf
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Schreiber
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.affiliation: Epic Sciences, San Diego, California.
authors.forename: Dena
authors.initials: D
authors.lastname: Marrinucci
authors.affiliation: Epic Sciences, San Diego, California.
authors.forename: Ryan
authors.initials: R
authors.lastname: Dittamore
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D015415:Biomarkers; D001706:Biopsy; D015331:Cohort Studies; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008297:Male; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers