1. CD73 expression in normal and pathological human hepatobiliopancreatic tissues.
- Author
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Sciarra A, Monteiro I, Ménétrier-Caux C, Caux C, Gilbert B, Halkic N, La Rosa S, Romero P, Sempoux C, and de Leval L
- Subjects
- 5'-Nucleotidase antagonists & inhibitors, Bile Duct Neoplasms mortality, Bile Duct Neoplasms pathology, Carcinoma, Hepatocellular chemistry, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Carcinoma, Pancreatic Ductal chemistry, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Cholangiocarcinoma chemistry, Cholangiocarcinoma mortality, Cholangiocarcinoma pathology, Epithelial-Mesenchymal Transition, GPI-Linked Proteins analysis, GPI-Linked Proteins antagonists & inhibitors, Humans, Immunohistochemistry, Liver Neoplasms mortality, Liver Neoplasms pathology, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Prognosis, 5'-Nucleotidase analysis, Bile Duct Neoplasms chemistry, Biliary Tract chemistry, Liver chemistry, Liver Neoplasms chemistry, Pancreas chemistry, Pancreatic Neoplasms chemistry
- Abstract
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.
- Published
- 2019
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