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, Paolo Bossi

Research output: Contribution to journalArticlepeer-review

Abstract

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 tumorinfiltrating 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 antitumor immune response in NPC metastatic patients.

Original languageEnglish
Pages (from-to)96184-96189
Number of pages6
JournalOncotarget
Volume8
Issue number56
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Denosumab
  • Epstein Barr Virus
  • Nasopharyngeal carcinoma
  • RANK
  • Tregs

ASJC Scopus subject areas

  • Oncology

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