title: Paired High-Content Analysis of Prostate Cancer Cells in Bone Marrow and Blood Characterizes Increased Androgen Receptor Expression in Tumor Cell Clusters.
abstract: Purpose:Recent studies demonstrate that prostate cancer clones from different metastatic sites are dynamically represented in the blood of patients over time, suggesting that the paired evaluation of tumor cells in circulation and bone marrow, the primary target for prostate cancer metastasis, may provide complementary information.Experimental Design:We adapted our single-cell high-content liquid biopsy platform to bone marrow aspirates (BMA) to concurrently identify and characterize prostate cancer cells in patients' blood and bone and thus discern features associated to tumorigenicity and dynamics of metastatic progression.Results:The incidence of tumor cells in BMAs increased as the disease advanced: 0% in biochemically recurrent (n= 52), 26% in newly diagnosed metastatic hormone-naïve (n= 26), and 39% in metastatic castration-resistant prostate cancer (mCRPC;n= 63) patients, and their number was often higher than in paired blood. Tumor cell detection in metastatic patients' BMAs was concordant but 45% more sensitive than using traditional histopathologic interpretation of core bone marrow biopsies. Tumor cell clusters were more prevalent and bigger in BMAs than in blood, expressed higher levels of the androgen receptor protein per tumor cell, and were prognostic in mCRPC. Moreover, the patterns of genomic copy number variation in single tumor cells in paired blood and BMAs showed significant inter- and intrapatient heterogeneity.Conclusions:Paired analysis of single prostate cancer cells in blood and bone shows promise for clinical application and provides complementary information. The high prevalence and prognostic significance of tumor cell clusters, particularly in BMAs, suggest that these structures are key mediators of prostate cancer's metastatic progression.Clin Cancer Res; 23(7); 1722-32. ©2016 AACR.
authors.affiliation: Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California.
authors.forename: Anders
authors.initials: A
authors.lastname: Carlsson
authors.affiliation: Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California. kuhn42@usc.edu azurita@mdanderson.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Kuhn
authors.affiliation: Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California.
authors.forename: Madelyn S
authors.initials: MS
authors.lastname: Luttgen
authors.affiliation: Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California.|Viterbi School of Engineering, University of Southern California, Los Angeles, California.
authors.forename: Kevin
authors.initials: K
authors.lastname: Keomanee-Dizon
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Patricia
authors.initials: P
authors.lastname: Troncoso
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Corn
authors.affiliation: Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California.
authors.forename: Anand
authors.initials: A
authors.lastname: Kolatkar
authors.affiliation: Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California.
authors.forename: James B
authors.initials: JB
authors.lastname: Hicks
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. kuhn42@usc.edu azurita@mdanderson.org.
authors.forename: Amado J
authors.initials: AJ
authors.lastname: Zurita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001854:Bone Marrow Cells / Q000473:pathology*; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000473:pathology; D011944:Receptors, Androgen / Q000097:blood*; D059010:Single-Cell Analysis
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen