Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

Javier Padillo-Ruiz,Paula Villanueva,Valeria Denninghoff,Inmaculada Gallego,Luis Marin,Miguel Angel Gomez-Bravo,Hada C Macher,Francisco Almoguera,Manuel Romero,Carmen Cepeda-Franco,Jose Tinoco,Francisco José Calero-Castro,Sheila Pereira,Gonzalo Suarez,Jose Maria Alamo,María José Serrano,Carmen Bernal,Francisco José García-Fernandez

doi:10.3390/cancers13246153

Abstract

Simple SummaryEffective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of circulating tumor cells and clusters from the central venous catheter and portal blood. Circulating tumor cells were isolated using an immunomagnetic selection and were detected by microscopy using immunocytochemistry staining. In conclusion, the circulating tumor cell number in portal blood identifies a death risk in patients with early pancreatic cancer.Background. Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). Methods. In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. Results. CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. Conclusions. CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers associated with poor prognosis and high mortality
This study aimed to correlate circulating tumor cell (CTC) and clusters count from portal vein (PV) and central venous catheter (CVC) with tumor grade, preoperatively tumor size/CA19-9, and vascular/lymphatic/neural invasion
We analyzed the prognostic value of both single CTC and clustered-CTC presented in the samples of patients with early-stage adenocarcinoma in the head of the pancreas

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers associated with poor prognosis and high mortality. Low-grade pancreatic cancers (G1) tend to grow and spread more slowly than high-grade (G3) cancers. G3 tends to have a poor prognosis compared to G1 or G2 cancers [1,2,3]. It is necessary to find prognostic markers that identify the minimal residual disease and predict the risk of relapse. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by

Objectives

Methods

Results

Discussion

Conclusion