ESOPHAGEAL ADENOCARCINOMA MICROENVIRONMENT: LEPTIN EXPRESSION IN PERITUMORAL ADIPOSE TISSUE IS ASSOCIATED WITH TUMOR GRADING AND STAGING, HIGHER IMMUNE INFILTRATION WITHIN THE TUMOR AND 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 Hospital 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. It is well-established that leptin is involved in the regulation of the inflammatory response. Thus, we aimed to assess the role of peritumoral adipose tissue leptin expression in esophageal adenocarcinoma (EAC) local immune response.
Methods: In a consecutive series of 60 patients with EAC, we measured leptin and adiponectin mRNA expression 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 and CD80+ antigen presenting cells infiltration. We correlated it to the pathological, clinical and immunological features of the EAC. Non-parametric statistics was used.
Results: We measured leptin mRNA expression in peritumoral adipose tissue of EAC patients and we observed a significant increase in patients treated with neoadjuvant therapy, in comparison with patients who did not receive neoadjuvant treatment (p=0.046). Moreover, leptin mRNA expression directly correlated with EAC grade and stage (rho=0.42, p=0.018 and rho=0.36, p=0.037, respectively). On the other hand, it also directly correlated with CD8+ lymphocyte and CD80+ antigen presenting cells infiltration within the tumor (rho=0.53, p=0.016 and rho=0.49, p=0.013, respectively). No significant correlations were observed with adiponectin peritumoral mRNA levels.
Conclusions: These results suggest that, in the peritumoral adipose tissue, leptin expression is associated to an advanced EAC stage and grade and to a higher immune infiltration, suggesting a potential role of adipose microenvironment in tumor development and local immune response.
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