Abstract 3916: Disease-specific markers may be used for the identification of disseminated tumor cells in the bone marrow of patients with prostate cancer
Authors: Toom Emma E. van der , Glavaris Stephanie A. , Gorin Michael A. , Verdone James A. , Pienta Kenneth J. , Chalfin Heather J. 
Published: July 2017

Introduction: The detection of microscopic disseminated disease in prostate cancer has largely been attempted with the study of circulating tumor cells (CTCs). Little is known about the character and clinical significance of disseminated tumor cells (DTCs) that have reached the bone marrow (BM) niche, and prior studies has relied on epithelial markers. Yet, it is known that such markers are also expressed on normal erythroid precursor cells in the BM, thus we developed an assay for prostate-specific DTC identification.

Materials and Methods: BM aspirates from 18 men with localized and 2 men with metastatic prostate cancer were collected at time of RP or clinic visit respectively, and processed with the AccuCyte system (RareCyte, Inc., Seattle, WA). Slides were immunostained with DAPI (nuclear), anti-pan-cytokeratin (epithelial), anti-CD45/CD66b/CD11b/CD14/CD34 (white blood cell), and the prostate-specific markers HOXB13 and NKX3.1 (prostate). DTCs were detected using the CyteFinder system. DTCs were required to have positive prostate channel staining and no white blood cell signal.

Results: DTCs were present in 89% (16/18) of patients at time of RP, with range 0 to 3592 cells/4 mL sample (average 270, median of 39.5). Two patients with metastatic prostate cancer had 52 and 105 DTCs/4mL BM (Table 1). Notably, only 5% of all DTCs were epithelial marker positive (CK+), and only 44% (8/18) of patients had any CK+ DTCs.

Conclusions: The RareCyte system is a promising selection-free system for DTCs detection that does not rely on epithelial markers. Here we report on a novel assay to distinguish DTCs from other cells in the bone marrow using the presumed prostate-specific markers HOXB13 and NKX3.1. Furthermore, we show that the majority of prostate-specific marker positive DTCs did not express the epithelial marker CK. Analyses of the association of DTC count with clinicopathologic variables are ongoing.

Table 1.Clinicopathologic Data and DTC Counts of the CohortBxRP GleasonMetastatic/LocalizedPSA# of DTCsCK+ DTCsCK- DTCs% of CK- DTCsGleason3+3=63+3=6Localized4.3000N/A3+3=63+3=6Localized6.3909100%3+3=64+3=7Localized3.948123675%3+3=63+4=7Localized3.4615015100%3+4=73+4=7Localized525025100%3+4=73+4=7Localized4.527918100%3+4=73+4=7Localized8.112012100%3+4=73+4=7Localized7.534034100%3+4=73+4=7Localized6.781216074%4+3=74+3=7Localized16.3114249079%4+3=74+3=7Localized5.91352710880%4+3=73+4=7Localized8.345045100%4+3=73+4=7Localized3.12254817779%4+3=74+3=7Localized942911731273%4+3=73+4=7Localized4.3359203592100%4+5=94+5=9Localized10.1000N/A4+5=94+4=8Localized9.1606100%4+5=94+5=9Localized9.46095185%4+5=9N/AMetastatic5.79105159086%4+5=9N/AMetastatic655284485%

Citation Format: Emma E. van der Toom, Stephanie A. Glavaris, Michael A. Gorin, James A. Verdone, Kenneth J. Pienta, Heather J. Chalfin. Disease-specific markers may be used for the identification of disseminated tumor cells in the bone marrow of patients with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3916. doi:10.1158/1538-7445.AM2017-3916