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04.01.2019 | Original Article

CD73 expression in normal and pathological human hepatobiliopancreatic tissues

verfasst von: Amedeo Sciarra, Inês Monteiro, Christine Ménétrier-Caux, Christophe Caux, Benoit Gilbert, Nermin Halkic, Stefano La Rosa, Pedro Romero, Christine Sempoux, Laurence de Leval

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 3/2019

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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.

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Titel: CD73 expression in normal and pathological human hepatobiliopancreatic tissues
verfasst von: Amedeo Sciarra
Inês Monteiro
Christine Ménétrier-Caux
Christophe Caux
Benoit Gilbert
Nermin Halkic
Stefano La Rosa
Pedro Romero
Christine Sempoux
Laurence de Leval
Publikationsdatum: 04.01.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 3/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2290-1

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CD73 expression in normal and pathological human hepatobiliopancreatic tissues

Abstract

Background

Patients and methods

Results

Conclusions

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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Abstract

Background

Patients and methods

Results

Conclusions

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