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PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors

Aims: To evaluate the biological significance of dense vascular networks associated with low-grade NENs, we assessed the impact of PDGFRα tissue expression in 77 GEP/NEN patients, associating PDGFRα expression with the morphological characterization in low-grade tumors. Methods and results: Paraffin...

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Autores principales: Cavalcanti, Elisabetta, Ignazzi, Antonia, De Michele, Francesco, Caruso, Maria Lucia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422502/
https://www.ncbi.nlm.nih.gov/pubmed/30346879
http://dx.doi.org/10.1080/15384047.2018.1529114
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author Cavalcanti, Elisabetta
Ignazzi, Antonia
De Michele, Francesco
Caruso, Maria Lucia
author_facet Cavalcanti, Elisabetta
Ignazzi, Antonia
De Michele, Francesco
Caruso, Maria Lucia
author_sort Cavalcanti, Elisabetta
collection PubMed
description Aims: To evaluate the biological significance of dense vascular networks associated with low-grade NENs, we assessed the impact of PDGFRα tissue expression in 77 GEP/NEN patients, associating PDGFRα expression with the morphological characterization in low-grade tumors. Methods and results: Paraffin-embedded specimens of 77 GEP- NEN tissues, collected from January 2006 to March 2018, were evaluated for PDGFRα tissue expression and correlations with clinicopathological characteristics. PDGFRα tissue expression was significantly correlated with grade and the NEN growth pattern (p < 0.001) but not with gender, primary site or lymph nodes metastatic status. PDGFRα staining was mainly localized in the vascular pole of the neuroendocrine cells and in Enterochromaffin (EC) cells. In particular PDGFRα tissue expression was significantly more expressed in G2 (p < 0.001) than G1 and G3 cases (p 0.004; p < 0.0002;) and correlated with an insular growth pattern. PDGFRα tissue expression was associated with the Ki67 index and we found a significant negative trend of association with the Ki67 proliferation index (P < 0.001): thus PDGFRα expression is referred to morphological and not to proliferative data. Conclusions: PDGFRα represents an effective target for new anti-angiogenic treatment in WD- GEP-NENs, in particular in G2 cases, and in G3 cases only when there is a mixed insular-acinar pattern. In this context, it is important to carefully delineate those tumors that might better respond to this type of treatment alone or in combination. Further investigation of the relationship between PD-L1 and PDGFRa is warranted, and may contribute to optimize the therapeutic approach in patients with GEP-NENs.
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spelling pubmed-64225022019-03-22 PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors Cavalcanti, Elisabetta Ignazzi, Antonia De Michele, Francesco Caruso, Maria Lucia Cancer Biol Ther Research Paper Aims: To evaluate the biological significance of dense vascular networks associated with low-grade NENs, we assessed the impact of PDGFRα tissue expression in 77 GEP/NEN patients, associating PDGFRα expression with the morphological characterization in low-grade tumors. Methods and results: Paraffin-embedded specimens of 77 GEP- NEN tissues, collected from January 2006 to March 2018, were evaluated for PDGFRα tissue expression and correlations with clinicopathological characteristics. PDGFRα tissue expression was significantly correlated with grade and the NEN growth pattern (p < 0.001) but not with gender, primary site or lymph nodes metastatic status. PDGFRα staining was mainly localized in the vascular pole of the neuroendocrine cells and in Enterochromaffin (EC) cells. In particular PDGFRα tissue expression was significantly more expressed in G2 (p < 0.001) than G1 and G3 cases (p 0.004; p < 0.0002;) and correlated with an insular growth pattern. PDGFRα tissue expression was associated with the Ki67 index and we found a significant negative trend of association with the Ki67 proliferation index (P < 0.001): thus PDGFRα expression is referred to morphological and not to proliferative data. Conclusions: PDGFRα represents an effective target for new anti-angiogenic treatment in WD- GEP-NENs, in particular in G2 cases, and in G3 cases only when there is a mixed insular-acinar pattern. In this context, it is important to carefully delineate those tumors that might better respond to this type of treatment alone or in combination. Further investigation of the relationship between PD-L1 and PDGFRa is warranted, and may contribute to optimize the therapeutic approach in patients with GEP-NENs. Taylor & Francis 2018-10-22 /pmc/articles/PMC6422502/ /pubmed/30346879 http://dx.doi.org/10.1080/15384047.2018.1529114 Text en © 2018 The Author(s). Published by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Research Paper
Cavalcanti, Elisabetta
Ignazzi, Antonia
De Michele, Francesco
Caruso, Maria Lucia
PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors
title PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors
title_full PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors
title_fullStr PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors
title_full_unstemmed PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors
title_short PDGFRα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors
title_sort pdgfrα expression as a novel therapeutic marker in well-differentiated neuroendocrine tumors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422502/
https://www.ncbi.nlm.nih.gov/pubmed/30346879
http://dx.doi.org/10.1080/15384047.2018.1529114
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