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 and/or the development of small cell or neuroendocrine tumor characteristics.
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As metastatic tumor biopsies are not always feasible and are difficult to repeat, we sought to evaluate noninvasive methods to identify patients transitioning towards a neuroendocrine phenotype (NEPC).
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.
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).
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2015 Dec 15 [Epub ahead of print]
Himisha Beltran, Adam Jendrisak, Mark Landers, Juan Miguel Mosquera, Myriam Kossai, Jessica Louw, Rachel Krupa, Ryon Graf, Nicole Schreiber, David M Nanus, Scott T Tagawa, Dena Marrinucci, Ryan Dittamore, Howard I Scher
Department of Medicine, Division of Hematology Oncology, Weill Cornell Medical College, Epic Sciences, Epic Sciences. , Epic Sciences, Epic Sciences. , Department of Pathology and Laboratory Medicine, Weill Cornell Medical College. , Department of Pathology and Laboratory Medicine, Weill Cornell Medical College. , Epic Sciences, Epic Sciences. , Epic Sciences, Epic Sciences. , Epic Sciences, Epic Sciences. , Medicine(Genitourinary Oncology Service), Memorial Sloan-Kettering Cancer Center. , Medicine, Weill Cornell Medical College (WCMC) of Cornell University. , Medicine:Hematology/Oncology and Urology, Weill Cornell Medical College. , Epic Sciences, Epic Sciences. , Epic Sciences, Epic Sciences. , Medicine(Genitourinary Oncology Service), Memorial Sloan-Kettering Cancer Center.