Role of circulating tumour cells in the management of the liver transplant patient with hepatocellular carcinoma
Felipe Alconchel1,2, Francisco Villalba2, Luis Sáenz2,3, María Isabel Sánchez-Lorencio2, David Ferreras1,2, Pedro Antonio Cascales-Campos1,2, Beatriz Febrero1,2, Laura Martínez-Alarcón1,2, Marta Jover1,2, Francisco Sánchez-Bueno1,2, Ricardo Robles-Campos1,2, Pablo Ramírez1,2.
1Surgery and Organ Transplantation, Virgen de la Arrixaca University Hospital, Murcia, Spain; 2Biomedical Research Institute of Murcia (IMIB-Virgen de la Arrixaca), Murcia, Spain; 3Rafael Méndez Hospital, Lorca, Spain
Introduction: For hepatocellular carcinoma (HCC), liver transplantation (LT) is considered a curative treatment, however, more than 10% of transplant recipients have recurrences within the first year. This suggests the existence of circulating-tumor-cells (CTC) that spread from a primary tumor and travel to peripheral blood and distant organs. Their detection and monitoring could be of great clinical value to an early prediction of recurrence as a real-time liquid biopsy. The aim of this study is to determine the relationship between CTC and clinicopathological variables and to compare the CTC-levels in patients with HCC before transplantation and at one and two years after surgery.
Methods: Peripheral blood was obtained from 34 patients with HCC included in the LT list. Immunomagnetic isolation of CTC was performed by the IsoFlux® System. Cell enrichment was stained with anti-CK, Hoechst-33342 and antiCD45, performing cell counting under a fluorescence microscope. The clinicopathological variables (number of tumors, vascular invasion, tumor necrosis and recurrence) were collected. Spearman's rho, Mann-Whitney and Wilcoxon test were used.
Results: We found statistically significant differences in the CTC-levels between patients with vascular invasion and those without (U=0; p=0.005) such that patients with vascular invasion had median levels of 539 CTC/10 mL (IR: 448-1768) and those without vascular invasion had median levels of 3 CTC/10 mL (IR:0- 31.25). Also we found a statistically significant decrease in post-transplant CTC-values at one year (Z= -2.672/ p=0.008) and two years (Z= -2.218/ p=0.027).
Conclusions: The median CTC-levels of the patients included in the study showed a downward trend after liver transplantation. Also, a significant difference was found in the levels of pre-transplant-CTC between patients with and without vascular invasion, these levels being significantly higher in patients with vascular invasion compared to those without vascular invasion. Detection of CTC may have a useful clinical implication in predicting the evolution of HCC after LT.
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