1. Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Germany.
2. Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Germany.
3. Tumorbank, Comprehensive Cancer Center Freiburg, University Medical Center Freiburg, Germany.
4. Institute for Surgical Pathology, University Medical Center Freiburg, Germany.
5. Department of General and Visceral Surgery, University Medical Center Freiburg, Germany.
6. Department of Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.
*Shared last authorship.
Introduction: Esophageal adenocarcinoma (EAC) often recurs systemically despite therapy with a curative aim. New diagnostic and therapeutic approaches are urgently needed. A promising field is liquid biopsy, meaning the investigation of tumor-associated cells in the peripheral blood, for example cancer-associated macrophage-like cells (CAML). The aim of this multicentric study was to investigate the presence and cytomorphological appearance of CAML in patients with non-metastatic and operable esophageal cancer.
Methods: Blood samples from 252 patients with locally advanced EAC were obtained before starting curative treatment including surgery, and then processed using ScreenCell® filtration devices. Cytological analysis was performed via May-Grünwald-Giemsa staining. CAML were defined by their morphological characteristics. We also performed immunofluorescence staining with the mesenchymal marker vimentin on a subset of our study cohort.
Results: We detected cytomorphologically heterogeneous CAML in 31.8% (n=80) patients. Their presence and cell count did not correlate significantly with pretherapeutic cTNM. Even in patients with small tumors and no lymph-node infiltration, cell counts were high. CAML showed heterogenous staining patterns for vimentin.
Conclusion: This is one of the first studies demonstrating the presence and phenotype of CAML in a uniquely broad cohort of EAC patients. As they are believed to be representatives of the inflammatory tumor microenvironment shed into the bloodstream, their presence in non-metastatic EAC is a promising finding.
Keywords: cancer-associated macrophage-like cell, CAML, esophageal adenocarcinoma, cytopathology, liquid biopsy, liquid biomarker