Arterial Blood, Rather Than Venous Blood, is a Better Source for Circulating Melanoma Cells

Abstract

Background: CTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients.

Methods: Blood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements.

Finding: CTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p = 0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases.

Interpretation: Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs.

Keywords: AKTi, AKT inhibitor; Ab, antibody; Arterial venous; BCNU, bischlorethylnitrosourea; CTC count; Circulating tumor cells; DEBDOX, drug-eluting beads with doxorubicin; EDTA, ethylenediaminetetraacetic acid; HMW-MAA, high molecular weight melanoma associated antigen; Hepatic metastasis; Ipi, ipilimumab; LN, lymph node; MEKi, MEK inhibitor; METi, MET inhibitor;; Peripheral venous; TACE, transarterial chemoembolization; Uveal melanoma; VPA, valproic acid; XRT, radiation therapy.

Fig. 1

Gallery of circulating tumor cells (CTCs) from the CellSearch Analyzer. Representative cell images obtained from patients using the melanoma detection kit. Figure shows representative images of CTCs from three patients on the CellTracks analyzer II. To be assigned as CTC, cells must have PE-stained nucleus (pseudocolored pink) and positive HMW-MAA staining (pseudocolored green).

Fig. 2

Numbers of CTC in peripheral arterial and venous blood specimens. Each column shows CTC numbers in arterial (red column) or venous (blue column) blood specimen in the same patient.

Fig. 3

Hepatic tumor volume and numbers of arterial CTC in patients with liver-only metastases. Each column showed the CTC numbers in individual patients. Blue columns: liver involvement with tumor < 20%; purple columns: 20–50%; and green columns: > 50%.

Fig. 4

Numbers of arterial CTC in uveal melanoma patients with and without extra-hepatic metastases. Numbers of CTC detected in patients who had hepatic and extra-hepatic metastases liver-only metastases were higher than those obtained from patients with hepatic metastases only (p = 0.003).