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J Urol. 2018 Jun;199(6):1494-1501. doi: 10.1016/j.juro.2018.01.033. Epub 2018 Jan 12.

Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow of Patients with Localized Disease Undergoing Radical Prostatectomy across Multiple Rare Cell Detection Platforms.

Author information

1
The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: heather.chalfin@jhmi.edu.
2
The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
3
Bridge Institute, University of Southern California, Los Angeles, California.
4
Department of Medicine, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
5
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
6
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Abstract

PURPOSE:

Prostate circulating tumor cells escape into peripheral blood and enter 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. We used multiple methodologies of disseminated tumor cell detection in bone marrow harvested at radical prostatectomy.

MATERIALS AND METHODS:

Bone marrow was harvested from 208 clinically localized cases, 16 controls and 5 metastatic cases with peripheral blood obtained from 37 metastatic cases. Samples were evaluated at 4 centers with 4 distinct platforms using antibody enrichment with the AdnaTest (Qiagen®) or VERSA (versatile exclusion based rare sample analysis), or whole sample interrogation with the RareCyte platform (Seattle, Washington) or HD-SCA (high definition single cell assay) using traditional epithelial markers and prostate specific markers. We investigated the sensitivity and specificity of these markers by evaluating expression levels in control and metastatic cases.

RESULTS:

EpCAM, NKX3.1 and AR were nonspecifically expressed in controls and in most samples using AdnaTest with no relation to perioperative variables. Only 1 patient with localized disease showed positive results for the prostate specific marker PSA. With the VERSA platform no localized case demonstrated disseminated tumor cells. With the RareCyte and HD-SCA platforms only a single patient had 1 disseminated tumor cell.

CONCLUSIONS:

Evaluation across multiple platforms revealed that epithelial markers are nonspecific in bone marrow and, thus, not suitable for disseminated tumor cell detection. Using prostate specific markers disseminated tumor cells were typically not detected in patients with localized prostate cancer.

KEYWORDS:

biomarkers; bone marrow; circulating; neoplasm metastasis; neoplastic cells; prostatic neoplasms; tumor

PMID:
29339080
PMCID:
PMC5964005
[Available on 2019-06-01]
DOI:
10.1016/j.juro.2018.01.033

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