ESOPHAGEAL ADENOCARCINOMA MICROENVIRONMENT: CD34 EXPRESSION IN PERITUMORAL ADIPOSE TISSUE IS ASSOCIATED WITH TUMOR NECROSIS AND IMPAIRED IMMUNE RESPONSE WITHIN THE TUMOR, AND IS DECREASED BY NEOADJUVANT TREATMENT
Elisabetta Trevellin*1, Amedeo Carraro2, Matteo Fassan3, Andromachi Kotsafti4, Matteo Cagol4, Luca Maria Saadeh4, Melania Scarpa4, Francesco Cavallin4, Umberto Tedeschi2, Massimo Rugge3, Roberto Vettor1, Marco Scarpa5
1Department of Medicine - Endocrine Metabolic Laboratory, University of Padova, Padova, Italy; 2Department of General Surgery and Odontoiatrics, University of Verona, Verona, Italy; 3Department of Medicine - Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy; 4Laboratory of Advanced Traslational Research, Veneto Institute of Oncology (IOV-IRCCS), Padova, Italy; 5General Surgery Unit, University Hospital of Padova, Padova, Italy
Background: Peritumoral microenvironment affects cancer development and chemoresistance, and visceral adipose tissue may play a critical role. Neoangiogenesis is a hallmark of carcinogenesis progression and CD34+ cells are normally found in endothelial progenitors and endothelial cells of blood vessels. We aimed to assess the role of adipose-specific CD34+ cells in esophageal adenocarcinoma (EAC) microenvironment.
Methods: In a consecutive series of 60 patients with EAC we measured immunohistochemical and mRNA expression of CD34 in sections of periesophageal (< 2 cm from cardia EAC) adipose tissue. Immune cancer infiltration was quantified with RT-PCR and immunohistochemistry: mRNA expression of Cd80, Cd86, Cd69, Cd38 and CD8+ lymphocyte infiltration. We correlated these data to the pathological, clinical and immunological features of the EAC. Non-parametric statistics was used.
Results: We observed a significantly decreased mRNA expression of CD34 in peritumoral adipose tissue of patients treated with neoadjuvant therapy, in comparison with patients who did not receive neoadjuvant treatment (p=0.002). Moreover, CD34 expression directly correlated with the extension of tumor necrosis (rho=0.39, p=0.029). On the other hand, it inversely correlated with CD86 (rho=-0.58, p=0.012) and CD38 (rho=-057, p=0.013) expression in tumor tissue.
Conclusions: These results suggest that in the peritumoral adipose tissue, CD34 expression is associated to higher tumor necrosis and its levels were influenced by neoadjuvant therapy. High CD34 levels were also associated with lower immune response within the tumor, suggesting a potential role of adipose-specific CD34+ cells in EAC development.
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