Oncotarget

Research Papers:

CD73 expression and clinical significance in human metastatic melanoma

Inês Monteiro, Selena Vigano, Mohamed Faouzi, Isabelle Treilleux, Olivier Michielin, Christine Ménétrier-Caux, Christophe Caux, Pedro Romero and Laurence de Leval _

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Oncotarget. 2018; 9:26659-26669. https://doi.org/10.18632/oncotarget.25426

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Abstract

Inês Monteiro1, Selena Vigano2, Mohamed Faouzi3, Isabelle Treilleux4, Olivier Michielin5, Christine Ménétrier-Caux6,7, Christophe Caux6,7, Pedro Romero2,* and Laurence de Leval1,*

1Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland

2Department of Oncology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

3Institute of Social and Preventive Medicine (IUMSP), University Hospital, Lausanne, Switzerland

4Anatomopathology Department, Centre Léon Bérard, Lyon, France

5Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland

6Université Claude Bernard Lyon 1, Centre de recherche en cancérologie de Lyon, Lyon, France

7Department of Innovation and Translational Research, Centre Léon Bérard, Lyon, France

*Co-last authors

Correspondence to:

Laurence de Leval, email: [email protected]

Keywords: CD73; ecto-5'-nucleotidase; immunohistochemistry; melanoma; prognosis

Received: February 12, 2018     Accepted: April 30, 2018     Published: June 01, 2018

ABSTRACT

Background: CD73 is an ectoenzyme involved in the production of adenosine. It exerts immunosuppressive and protumoral roles and has emerged as a potential immuno-oncology target.

Results: CD73 expression was detected in TC in 54% of melanoma metastases, involving < 50% TC in the majority of the cases, with variable intensity. CD73 expression was significantly associated with a lower Breslow’s depth of the primary lesion and was more frequent in patients having received prior non-surgical therapies. In an adjusted analysis, CD73 expression in TC (H-score > 37.5 or intensity > 1) significantly correlated to decreased overall survival (OS) from biopsy. Of the samples containing TIMC, 35% presented CD73+ TIMC. Highly infiltrated tumors were more likely to contain CD73+ TIMC. CD73 expression in TIMC (percentage ≥1%) significantly correlated with improved OS from biopsy.

Conclusions: Immunohistochemistry detected CD73 expression in more than half of metastatic melanomas. While CD73 expression in TC significantly correlated with decreased OS, CD73 expression in TIMC significantly associated with improved OS. These results encourage the study of anti-CD73 therapies for metastatic melanoma patients.

Methods: CD73 expression was assessed by immunohistochemistry in metastatic melanomas from 114 patients. Immunostainings were evaluated in tumor cells (TC) (percentage, intensity (1–3) and H-score) and in tumor-infiltrating mononuclear cells (TIMC) (percentage).


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