Prostate circulating tumor cells escape into the peripheral blood and enter the bone marrow as disseminated tumor cells, representing an early step before conventionally detectable metastasis. It is unclear how frequently this occurs in localized disease, and existing detection methods rely on epithelial markers with low specificity and sensitivity. Here we employed multiple methodologies of disseminated tumor cell detection in bone marrow harvested at radical prostatectomy.
Bone marrow was harvested from 208 clinically localized patients, 16 controls, and 5 metastatic patients, with peripheral blood from 37 metastatic patients. Samples were evaluated at 4 separate centers with 4 distinct platforms that utilized antibody enrichment (AdnaTest, VERSA) or whole sample interrogation (RareCyte, HD-SCA), using traditional epithelial markers and prostate-specific markers. We investigated the sensitivity and specificity of these markers by evaluating their expression levels in both control and metastatic patients.
EpCAM, NKX3.1, and AR were non-specifically expressed in the controls and a majority of all samples with the AdnaTest, with no relation to perioperative variables. Only 1 patient with localized disease was positive for the prostate-specific marker PSA. With the VERSA platform, no localized patient had disseminated tumor cells. With both the RareCyte and HD-SCA platforms, only a single patient had 1 disseminated tumor cell.
Evaluation across multiple platforms revealed that epithelial markers are non-specific in the bone marrow and thus not suitable for disseminated tumor cell detection. Using prostate-specific markers, disseminated tumor cells were typically not detected in localized prostate cancer patients.
The Journal of urology. 2018 Jan 12 [Epub ahead of print]
Heather J Chalfin, Stephanie A Glavaris, Paymaneh D Malihi, Jamie M Sperger, Michael A Gorin, Changxue Lu, C Rory Goodwin, Yan Chen, Emily A Caruso, Ruth Dumpit, Peter Kuhn, Joshua M Lang, Peter S Nelson, Jun Luo, Kenneth J Pienta
The James Buchanan Brady Urological Institute and Department of Urology. Electronic address: ., The James Buchanan Brady Urological Institute and Department of Urology., The Bridge@USC, University of Southern California., University of Wisconsin Carbone Cancer Center, Department of Medicine., The Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287., Fred Hutchinson Cancer Research Center, Division of Human Biology.