The Prognostic Role of CD73/A2AR Expression and Tumor Immune Response in Periampullary Carcinoma Subtypes

INTRODUCTION: Periampullary adenocarcinoma (PAAC) is a rare, lethal heterogeneous group of malignancy that differs in their molecular phenotypes. Ecto-5′-nucleotidase (CD73)/adenosine A2A Receptor (A2AR) pathway has shown an emerging role in cancer therapy through modulating the immune response. Therefore, this study aimed to explore the functional role of CD73 and A2AR in pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AC). Material and methods: An immunohistochemical study for CD73 and A2AR carried on 48 PDAC cases, 21 AC cases and 34 adjacent non-tumor tissues that were taken from the farthest point of normal pancreatic tissue away from the tumor. RESULTS: CD73 was overexpressed in the PDAC (p < 0.001), and AC (p = 0.004) groups compared to their non-tumor tissues. However, A2AR was overexpressed in the PDAC group (p = 0.003) but not in the AC group (p = 0.359) compared to non-tumor tissue. In the PDAC group, CD73 overexpression was significantly associated with longer overall survival (p = 0.018). In contrary, A2AR overexpression was significantly associated with high grade (p = 0.001) and late- stage (p = 0.01). Both markers had no prognostic impact on AC. In the meantime, tumor immune response showed a negative prognostic role in PDAC and AC. The prognostic role of tumor immune response in the PDAC group was strongly modulated by CD73 and A2AR expression. CONCLUSIONS: PDAC and AC shared CD73 Overexpression while A2AR was overexpressed in PDAC only. In PDAC, CD73 and A2AR showed an opposed prognostic effect but both had no prognostic impact on AC. In addition, tumor immune response showed a controversial impact on the prognosis of PDAC and AC.