Research Papers:

RANK expression in EBV positive nasopharyngeal carcinoma metastasis: a ready-to-treat target?

Carlo Resteghini, Salvatore Alfieri, Pasquale Quattrone, Francesca Dominoni, Giovanna Garzone, Ester Orlandi, Laura Locati, Cristiana Bergamini, Donata Galbiati, Nicola Alessandro Iacovelli, Carlo Fallai, Lisa Licitra and Paolo Bossi _

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Oncotarget. 2017; 8:96184-96189. https://doi.org/10.18632/oncotarget.21856

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Carlo Resteghini1, Salvatore Alfieri1, Pasquale Quattrone2, Francesca Dominoni2, Giovanna Garzone2, Ester Orlandi3, Laura Locati1, Cristiana Bergamini1, Donata Galbiati1, Nicola Alessandro Iacovelli3, Carlo Fallai3, Lisa Licitra1 and Paolo Bossi1

1Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy

2Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy

3Radiation Oncology Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy

Correspondence to:

Paolo Bossi, email: [email protected]

Keywords: RANK; nasopharyngeal carcinoma; Epstein Barr virus; Tregs; denosumab

Received: March 02, 2017     Accepted: August 26, 2017     Published: October 16, 2017


Epstein Barr Virus (EBV) related Nasopharyngeal Carcinoma (NPC), is an highly chemo- and radiosensitive endemic malignancy in southeast Asia. More than one third of locally advanced cases relapse after curative treatment, especially because of bone, liver and lung metastases. Lymphocyte sub-populations favour EBV-associated carcinogenesis and tumour progression and several strategies aim to reverse this phenomenon. Receptor activator of NF-kB (RANK) and its Ligand (RANKL), key regulator of bone metabolisms, are expressed in several malignancies and tumor-infiltrating Tregs. We collected 17 paired FFPE specimen of primary and metachronous metastatic or regionally relapsed EBV related NPC and evaluated RANK expression by immunohistochemistry. All primary tumour specimens resulted not evaluable whereas all metastatic specimens, regardless of sites, showed high RANK IHC expression in the tumor with no staining in normal surrounding tissues. This observation deserves further clarifications and could open the way to trials testing the hypotesis that targeting the RANK/RANKL pathway with denosumab, an already available, clinically approved monoclonal antibody for metastatic bone lesions, might restore proper anti-tumor immune response in NPC metastatic patients.

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