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The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases

Due to the relatively high recurrence rate and the destructive nature of the tumor, the treatment of giant cell tumor is still a challenge. Denosumab appeared to be a promising candidate as a therapeutic drug. However, several studies have reported that tumors can recur during/after treatment with d...

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Autores principales: Antal, Imre, Pápai, Zsuzsanna, Szendrői, Miklós, Perlaky, Tamás, Dezső, Katalin, Lippai, Zoltán, Sápi, Zoltán
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448856/
https://www.ncbi.nlm.nih.gov/pubmed/36091939
http://dx.doi.org/10.3389/pore.2022.1610633
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author Antal, Imre
Pápai, Zsuzsanna
Szendrői, Miklós
Perlaky, Tamás
Dezső, Katalin
Lippai, Zoltán
Sápi, Zoltán
author_facet Antal, Imre
Pápai, Zsuzsanna
Szendrői, Miklós
Perlaky, Tamás
Dezső, Katalin
Lippai, Zoltán
Sápi, Zoltán
author_sort Antal, Imre
collection PubMed
description Due to the relatively high recurrence rate and the destructive nature of the tumor, the treatment of giant cell tumor is still a challenge. Denosumab appeared to be a promising candidate as a therapeutic drug. However, several studies have reported that tumors can recur during/after treatment with denosumab. Based on activated receptor tyrosine kinase signaling pattern of the stromal/tumor cells, a combination treatment with denosumab and sunitinib has recently been proposed to inhibit recurrences. This prompted us to investigate the PDGFRβ expression of five denosumab treated cases using both primary and recurrent tumors during and after denosumab treatment. In addition, to recognise morphological changes, immunohistochemical analysis of H3F3A and PDGFRβ was also performed. As an effect of denosumab treatment, the permanent absence of giant cells associated with severe to mild fibrosis was the most consistent morphological change, but H3F3A positive stromal/tumor cells were observed in all cases. Furthermore, an increased immunopositivity of PDGFRβ in stromal/tumor cells was evident in all recurrent cases during denosumab treatment. Upon tumor recurrence (after the discontinuation of denosumab treatment) the intensity of PDGFRβ immunostaining in stromal/tumor cells was restored/decreased. Our results confirm (for the first time) the activation of PDGFRβ on mononuclear stromal/tumor cells at protein level as an effect of denosumab treatment, which has so far only been demonstrated by phosphoprotein array analysis (protein lysates). The decreased PDGFRβ activity after the discontinuation of denosumab treatmeant and the increased PDGFRβ activity during denosumab treatment underlines the need for denosumab and sunitinib combination therapy.
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spelling pubmed-94488562022-09-08 The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases Antal, Imre Pápai, Zsuzsanna Szendrői, Miklós Perlaky, Tamás Dezső, Katalin Lippai, Zoltán Sápi, Zoltán Pathol Oncol Res Pathology and Oncology Archive Due to the relatively high recurrence rate and the destructive nature of the tumor, the treatment of giant cell tumor is still a challenge. Denosumab appeared to be a promising candidate as a therapeutic drug. However, several studies have reported that tumors can recur during/after treatment with denosumab. Based on activated receptor tyrosine kinase signaling pattern of the stromal/tumor cells, a combination treatment with denosumab and sunitinib has recently been proposed to inhibit recurrences. This prompted us to investigate the PDGFRβ expression of five denosumab treated cases using both primary and recurrent tumors during and after denosumab treatment. In addition, to recognise morphological changes, immunohistochemical analysis of H3F3A and PDGFRβ was also performed. As an effect of denosumab treatment, the permanent absence of giant cells associated with severe to mild fibrosis was the most consistent morphological change, but H3F3A positive stromal/tumor cells were observed in all cases. Furthermore, an increased immunopositivity of PDGFRβ in stromal/tumor cells was evident in all recurrent cases during denosumab treatment. Upon tumor recurrence (after the discontinuation of denosumab treatment) the intensity of PDGFRβ immunostaining in stromal/tumor cells was restored/decreased. Our results confirm (for the first time) the activation of PDGFRβ on mononuclear stromal/tumor cells at protein level as an effect of denosumab treatment, which has so far only been demonstrated by phosphoprotein array analysis (protein lysates). The decreased PDGFRβ activity after the discontinuation of denosumab treatmeant and the increased PDGFRβ activity during denosumab treatment underlines the need for denosumab and sunitinib combination therapy. Frontiers Media S.A. 2022-08-24 /pmc/articles/PMC9448856/ /pubmed/36091939 http://dx.doi.org/10.3389/pore.2022.1610633 Text en Copyright © 2022 Antal, Pápai, Szendrői, Perlaky, Dezső, Lippai and Sápi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pathology and Oncology Archive
Antal, Imre
Pápai, Zsuzsanna
Szendrői, Miklós
Perlaky, Tamás
Dezső, Katalin
Lippai, Zoltán
Sápi, Zoltán
The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases
title The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases
title_full The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases
title_fullStr The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases
title_full_unstemmed The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases
title_short The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases
title_sort activation of pdgfrβ on mononuclear stromal/tumor cells in giant cell tumor of bone after denosumab treatment. an immunohistochemical study of five cases
topic Pathology and Oncology Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448856/
https://www.ncbi.nlm.nih.gov/pubmed/36091939
http://dx.doi.org/10.3389/pore.2022.1610633
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