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 language | English |
|---|---|
| Pages (from-to) | 96184-96189 |
| Number of pages | 6 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 56 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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Keywords
- Denosumab
- Epstein Barr Virus
- Nasopharyngeal carcinoma
- RANK
- Tregs
ASJC Scopus subject areas
- Oncology
Cite this
RANK expression in EBV positive nasopharyngeal carcinoma metastasis : A ready-to-treat target? / Resteghini, Carlo; Alfieri, Salvatore; Quattrone, Pasquale; Dominoni, Francesca; Garzone, Giovanna; Orlandi, Ester; Locati, Laura; Bergamini, Cristiana; Galbiati, Donata; Iacovelli, Nicola Alessandro; Fallai, Carlo; Licitra, Lisa; Bossi, Paolo.
In: Oncotarget, Vol. 8, No. 56, 01.01.2017, p. 96184-96189.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - RANK expression in EBV positive nasopharyngeal carcinoma metastasis
T2 - A ready-to-treat target?
AU - Resteghini, Carlo
AU - Alfieri, Salvatore
AU - Quattrone, Pasquale
AU - Dominoni, Francesca
AU - Garzone, Giovanna
AU - Orlandi, Ester
AU - Locati, Laura
AU - Bergamini, Cristiana
AU - Galbiati, Donata
AU - Iacovelli, Nicola Alessandro
AU - Fallai, Carlo
AU - Licitra, Lisa
AU - Bossi, Paolo
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Denosumab
KW - Epstein Barr Virus
KW - Nasopharyngeal carcinoma
KW - RANK
KW - Tregs
UR - http://www.scopus.com/inward/record.url?scp=85033387656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85033387656&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.21856
DO - 10.18632/oncotarget.21856
M3 - Article
AN - SCOPUS:85033387656
VL - 8
SP - 96184
EP - 96189
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 56
ER -