Abstract 384: Detection of circulating melanoma cells in paired arterial and venous specimens from uveal melanoma patients with hepatic metastatic
Authors: Terai Mizue , Mu Zhaomei , Eschelman David , Gonsalves Carin , Kageyama Ken , Mastrangelo Michael J. , Orloff Marlana , Weight Ryan , Cristofanilli Massimo , Sato Takami 
Published: August 2015

Background: Circulating tumor cells (CTCs) represent a surrogate biomarker for hematogenous metastases. The detection of CTCs has gained increasing interest for prediction of clinical outcome. However, it remains to be determined whether uveal melanoma cells circulating in a peripheral vein predict systemic recurrence and poorer overall prognosis.

Uveal melanoma, the most common primary cancer of the eye in adults, is unique in that the uveal tract is devoid of lymphatics. Since systemic recurrence develops exclusively via hematogenous spread, patients with uveal melanomas present a special opportunity to explore the prognostic potential of CTCs. Although the lung is the first organ through which venous drainage from the affected eye passes and indeed the only organ through which all venous blood must pass, 80-95% of systemic metastases are found first in the liver without development of lung metastases. To address these issues, we investigated the numbers of CTCs in paired arterial (femoral) and venous (antecubital) blood specimens obtained from uveal melanoma patients with hepatic metastases.

Methods: CTCs in blood specimens were measured in 17 uveal melanoma patients with multiple hepatic metastases, including 10 patients with liver-only metastases and 7 patients with hepatic and extra-hepatic metastases. Peripheral arterial and venous blood specimens were collected at the same time prior to liver directed treatment. CTCs were analyzed using CellTracks Circulating melanoma Cell Kit by CellSearch System. The clinical information and sources of blood specimens were blinded when CTCs were analyzed.

Result: CTCs were detectable from all 17 arterial blood specimens (100%) (median 5, range 1 to 168). In contrast, much smaller numbers of CTCs were detectable in 52.9% (9/17) of venous blood specimens (median 1, range 0 to 8) from the same patients. In terms of degree of tumor burden, patients who have hepatic as well as extra-hepatic metastasis showed higher numbers of arterial CTCs (median 12, range 5 to 168), compared to patients who have liver-only metastasis (median 4, range 1 to 11). More importantly, there is no significant correlation between numbers of arterial CTCs and the degree of tumor volume in the liver in patients who have liver-only metastases.

Conclusions: Using this technology, the detection of uveal melanoma cells in peripheral blood is feasible. Peripheral capillary beds effectively filter CTCs from venous blood; thus venous blood might not be the best source for measurement of CTCs in patients with metastatic uveal melanoma. The paucity of clinically evident non-hepatic metastases despite the effective filtration by peripheral capillary beds remains unexplained and may be a demonstration of the “seed and soil” hypothesis. CTCs are a non-invasive source of uveal melanoma cells for evaluating tumor biology. Further investigation is warranted.

Citation Format: Mizue Terai, Zhaomei Mu, David Eschelman, Carin Gonsalves, Ken Kageyama, Michael J. Mastrangelo, Marlana Orloff, Ryan Weight, Massimo Cristofanilli, Takami Sato. Detection of circulating melanoma cells in paired arterial and venous specimens from uveal melanoma patients with hepatic metastatic. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 384. doi:10.1158/1538-7445.AM2015-384