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Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are characterized by mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor α) that may be efficiently targeted by tyrosine kinase inhibitors (TKI). Notwithstanding the ea...

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Autores principales: Rizzo, Francesca Maria, Palmirotta, Raffaele, Marzullo, Andrea, Resta, Nicoletta, Cives, Mauro, Tucci, Marco, Silvestris, Franco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750215/
https://www.ncbi.nlm.nih.gov/pubmed/26867653
http://dx.doi.org/10.1186/s12885-016-2111-x
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author Rizzo, Francesca Maria
Palmirotta, Raffaele
Marzullo, Andrea
Resta, Nicoletta
Cives, Mauro
Tucci, Marco
Silvestris, Franco
author_facet Rizzo, Francesca Maria
Palmirotta, Raffaele
Marzullo, Andrea
Resta, Nicoletta
Cives, Mauro
Tucci, Marco
Silvestris, Franco
author_sort Rizzo, Francesca Maria
collection PubMed
description BACKGROUND: Gastrointestinal stromal tumors (GISTs) are characterized by mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor α) that may be efficiently targeted by tyrosine kinase inhibitors (TKI). Notwithstanding the early responsiveness to TKI, the majority of GISTs progress, imposing the need for alternative therapeutic strategies. DOG1 (discovered on GIST-1) shows a higher sensitivity as a diagnostic marker than KIT, however its prognostic role has been little investigated. METHODS: We evaluated DOG1 expression by immunohistochemistry (IHC) in 59 patients with GISTs, and correlated its levels with clinical and pathological features as well as mutational status. Kaplan-Meier analysis was also applied to assess correlations of the staining score with patient recurrence-free survival (RFS). RESULTS: DOG1 was expressed in 66 % of CD117(+) GISTs and highly associated with tumor size and the rate of wild-type tumors. Kaplan-Meier survival analysis showed that a strong DOG1 expression demonstrated by IHC correlated with a worse 2-year RFS rate, suggesting its potential ability to predict GISTs with poor prognosis. CONCLUSIONS: These findings suggest a prognostic role for DOG1, as well as its potential for inclusion in the criteria for risk stratification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2111-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-47502152016-02-12 Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations Rizzo, Francesca Maria Palmirotta, Raffaele Marzullo, Andrea Resta, Nicoletta Cives, Mauro Tucci, Marco Silvestris, Franco BMC Cancer Research Article BACKGROUND: Gastrointestinal stromal tumors (GISTs) are characterized by mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor α) that may be efficiently targeted by tyrosine kinase inhibitors (TKI). Notwithstanding the early responsiveness to TKI, the majority of GISTs progress, imposing the need for alternative therapeutic strategies. DOG1 (discovered on GIST-1) shows a higher sensitivity as a diagnostic marker than KIT, however its prognostic role has been little investigated. METHODS: We evaluated DOG1 expression by immunohistochemistry (IHC) in 59 patients with GISTs, and correlated its levels with clinical and pathological features as well as mutational status. Kaplan-Meier analysis was also applied to assess correlations of the staining score with patient recurrence-free survival (RFS). RESULTS: DOG1 was expressed in 66 % of CD117(+) GISTs and highly associated with tumor size and the rate of wild-type tumors. Kaplan-Meier survival analysis showed that a strong DOG1 expression demonstrated by IHC correlated with a worse 2-year RFS rate, suggesting its potential ability to predict GISTs with poor prognosis. CONCLUSIONS: These findings suggest a prognostic role for DOG1, as well as its potential for inclusion in the criteria for risk stratification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2111-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-11 /pmc/articles/PMC4750215/ /pubmed/26867653 http://dx.doi.org/10.1186/s12885-016-2111-x Text en © Rizzo et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Rizzo, Francesca Maria
Palmirotta, Raffaele
Marzullo, Andrea
Resta, Nicoletta
Cives, Mauro
Tucci, Marco
Silvestris, Franco
Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations
title Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations
title_full Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations
title_fullStr Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations
title_full_unstemmed Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations
title_short Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations
title_sort parallelism of dog1 expression with recurrence risk in gastrointestinal stromal tumors bearing kit or pdgfra mutations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750215/
https://www.ncbi.nlm.nih.gov/pubmed/26867653
http://dx.doi.org/10.1186/s12885-016-2111-x
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