CD73 expression in normal and pathological human hepatobiliopancreatic tissues

• Published in: Cancer Immunology, Immunotherapy Vol. 68; no. 3; pp. 467 - 478
• Main Authors: Sciarra, Amedeo, Monteiro, Inês, Ménétrier-Caux, Christine, Caux, Christophe, Gilbert, Benoit, Halkic, Nermin, La Rosa, Stefano, Romero, Pedro, Sempoux, Christine, de Leval, Laurence
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2019; Springer Nature B.V; Springer Verlag
• Subjects: 5'-Nucleotidase - analysis; 5'-Nucleotidase - antagonists & inhibitors; Adenocarcinoma; Adenosine; AMP; Bile Duct Neoplasms - chemistry; Bile Duct Neoplasms - mortality; Bile Duct Neoplasms - pathology; Biliary tract; Biliary Tract - chemistry; Cancer immunotherapy; Cancer Research; Carcinoma; Carcinoma, Hepatocellular - chemistry; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Carcinoma, Pancreatic Ductal - chemistry; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; CD73 antigen; Cholangiocarcinoma - chemistry; Cholangiocarcinoma - mortality; Cholangiocarcinoma - pathology; E-cadherin; Ectonucleotidase; Epithelial-Mesenchymal Transition; GPI-Linked Proteins - analysis; GPI-Linked Proteins - antagonists & inhibitors; Hepatocellular carcinoma; Hepatocytes; Humans; Immunohistochemistry; Immunological tolerance; Immunology; Immunotherapy; Invasiveness; Life Sciences; Liver - chemistry; Liver cancer; Liver Neoplasms - chemistry; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Medicine; Medicine & Public Health; Neoplasia; Neuroendocrine tumors; Oncology; Original; Original Article; Pancreas; Pancreas - chemistry; Pancreatic cancer; Pancreatic carcinoma; Pancreatic Neoplasms - chemistry; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Patients; Prognosis; Tumor cells; Tumors; Immunohistochemistry; Hepatocellular carcinoma; CD73; Pancreatic carcinoma; Ecto-5′-nucleotidase; Cholangiocarcinoma
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-018-2290-1

Background
The tumor-expressed CD73 ectonucleotidase generates immune tolerance and promotes invasiveness via adenosine production from degradation of AMP. While anti-CD73 blockade treatment is a promising tool in cancer immunotherapy, a characterization of CD73 expression in human hepatobiliopancreatic system is lacking.
Patients and methods
CD73 expression was investigated by immunohistochemistry in a variety of non-neoplastic and neoplastic conditions of the liver, pancreas, and biliary tract.
Results
CD73 was expressed in normal hepatobiliopancreatic tissues with subcellular-specific patterns of staining: canalicular in hepatocytes, and apical in cholangiocytes and pancreatic ducts. CD73 was present in all hepatocellular carcinoma (HCC), in all pancreatic ductal adenocarcinoma (PDAC), and in the majority of intra and extrahepatic cholangiocellular carcinomas, whereas it was detected only in a subset of pancreatic neuroendocrine neoplasms and almost absent in acinar cell carcinoma. In addition to the canonical pattern of staining, an aberrant membranous and/or cytoplasmic expression was observed in invasive lesions, especially in HCC and PDAC. These two entities were also characterized by a higher extent and intensity of staining as compared to other hepatobiliopancreatic neoplasms. In PDAC, aberrant CD73 expression was inversely correlated with differentiation (
p
 < 0.01) and was helpful to identify isolated discohesive tumor cells. In addition, increased CD73 expression was associated with reduced overall survival (HR 1.013) and loss of E-Cadherin.
Conclusions
Consistent CD73 expression supports the rationale for testing anti-CD73 therapies in patients with hepatobiliopancreatic malignancies. Specific patterns of expression could also be of help in the routine diagnostic workup.