Comparative Analysis of Blood and Bone Marrow for the Detection of Circulating and Disseminated Tumor Cells and Their Prognostic and Predictive Value in Esophageal Cancer Patients.

Florian Richter,Annette Baratay,Holger Kalthoff,Jan-Hendrik Egberts,Thomas Becker,Susanne Sebens,Christian Röder

doi:10.3390/jcm9082674

Abstract

Hematogenic tumor cell spread is a key event in metastasis. However, the clinical significance of circulating tumor cells (CTC) in the blood and disseminated tumor cells (DTC) in bone marrow is still not fully understood. Here, the presence of DTC and CTC in esophageal cancer (EC) patients and its correlation with clinical parameters was investigated to evaluate the CTC/DTC prognostic value in EC. This study included 77 EC patients with complete surgical tumor resection. CTC and DTC were analyzed in blood and bone marrow using nested CK20 reverse transcription-nested polymerase chain reaction (RT-PCR) and findings were correlated with clinical data. Twenty-seven of 76 patients (36.5%) showed CK20 positivity in the blood, 19 of 61 patients (31.1%) in bone marrow, and 40 (51.9%) of 77 patients were positive in either blood or bone marrow or both. In multivariate analyses, only the DTC status emerged as independent predictor of overall and tumor specific survival. Our study revealed that, while the presence of CTC in blood is not associated with a worse prognosis, DTC detection in the bone marrow is a highly specific and independent prognostic marker in EC patients. Larger cohort studies could unravel how this finding can be translated into improved therapy management in EC.

Highlights

Esophageal cancer (EC) is still one of the most aggressive epithelial tumors and its incidence is increasing [1]
In order to investigate whether detection of CK20 expression in liquid biopsies is an independent prognostic factor for EC patients, multivariate analyses using the Cox regression model were performed and calculated, using the stepwise inclusion method and the likelihood quotient (LQ) method
CK20 positivity in bone marrow was included in the calculations for overall and tumor-specific survival, whereas CK20 messenger ribonucleic acid (mRNA) detection in blood samples was not

Summary

Introduction

Esophageal cancer (EC) is still one of the most aggressive epithelial tumors and its incidence is increasing [1]. The mean 5-year survival rate is between 10–25%, making it one of the carcinomas with a poor prognosis and a mortality rate of up to 90% [2], which can be partly explained by the fact that only one in seven tumors is detected at an early stage (T1) [3,4]. Pre-operative radiologic and endoscopic procedures are performed in order to detect visible metastases of esophageal carcinomas, and to perform a first therapy decision. Pre-operative diagnostics serve to differentiate whether endoscopic removal of the tumor is possible, or whether surgical resection is necessary [5,6]. In case of a locally advanced tumor disease, a surgical esophago-lymphadenectomy is a major component of a multimodal therapy [7,8]. The preferred curative treatment of EC is transthoracic esophagectomy with

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