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Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling

Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation and also in the heart. They are morphologically similar to other spindle cell, poorly differentiated sarcomas. The prognosis is poor and depends mainly on surgical opt...

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Autores principales: Giner, Francisco, Machado, Isidro, Rubio-Martínez, Luis Alberto, López-Guerrero, José Antonio, Claramunt-Alonso, Reyes, Navarro, Samuel, Ferrández, Antonio, Mayordomo-Aranda, Empar, Llombart-Bosch, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141691/
https://www.ncbi.nlm.nih.gov/pubmed/37108696
http://dx.doi.org/10.3390/ijms24087535
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author Giner, Francisco
Machado, Isidro
Rubio-Martínez, Luis Alberto
López-Guerrero, José Antonio
Claramunt-Alonso, Reyes
Navarro, Samuel
Ferrández, Antonio
Mayordomo-Aranda, Empar
Llombart-Bosch, Antonio
author_facet Giner, Francisco
Machado, Isidro
Rubio-Martínez, Luis Alberto
López-Guerrero, José Antonio
Claramunt-Alonso, Reyes
Navarro, Samuel
Ferrández, Antonio
Mayordomo-Aranda, Empar
Llombart-Bosch, Antonio
author_sort Giner, Francisco
collection PubMed
description Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation and also in the heart. They are morphologically similar to other spindle cell, poorly differentiated sarcomas. The prognosis is poor and depends mainly on surgical options. Three cases of IS were collected from two institutions. Clinical data were retrieved and histological study was performed. A wide immunohistochemical panel was analyzed. FISH of MDM2 gene was performed, and a molecular study with NGS was implemented in all cases. The mean age of our cases was 54 years. Histologically, the tumors presented a diffuse growth pattern with heterogeneous atypical epithelioid or spindle cells and extensive thrombosed areas. All cases presented intense immunoexpression for MDM2, CDK4, CD117, c-myc, PDGFRA, and p16. PDGFRA, HTERT, and pan-TRK gained expression, while p16 lost intensity, being weaker in both the local recurrences and xenografts. The three cases showed amplification of MDM2 by FISH. NGS analysis revealed amplifications in the CDK4, PDGFRA, and KIT genes, together with BRAF mutation and KRAS amplification. P16 was expressed in all cases, losing intensity in local recurrence and xenografts. Two new alterations, a BRAF mutation and a KRAS amplification, were detected by NGS in different tumors, opening up new therapeutic options for these patients.
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spelling pubmed-101416912023-04-29 Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling Giner, Francisco Machado, Isidro Rubio-Martínez, Luis Alberto López-Guerrero, José Antonio Claramunt-Alonso, Reyes Navarro, Samuel Ferrández, Antonio Mayordomo-Aranda, Empar Llombart-Bosch, Antonio Int J Mol Sci Article Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation and also in the heart. They are morphologically similar to other spindle cell, poorly differentiated sarcomas. The prognosis is poor and depends mainly on surgical options. Three cases of IS were collected from two institutions. Clinical data were retrieved and histological study was performed. A wide immunohistochemical panel was analyzed. FISH of MDM2 gene was performed, and a molecular study with NGS was implemented in all cases. The mean age of our cases was 54 years. Histologically, the tumors presented a diffuse growth pattern with heterogeneous atypical epithelioid or spindle cells and extensive thrombosed areas. All cases presented intense immunoexpression for MDM2, CDK4, CD117, c-myc, PDGFRA, and p16. PDGFRA, HTERT, and pan-TRK gained expression, while p16 lost intensity, being weaker in both the local recurrences and xenografts. The three cases showed amplification of MDM2 by FISH. NGS analysis revealed amplifications in the CDK4, PDGFRA, and KIT genes, together with BRAF mutation and KRAS amplification. P16 was expressed in all cases, losing intensity in local recurrence and xenografts. Two new alterations, a BRAF mutation and a KRAS amplification, were detected by NGS in different tumors, opening up new therapeutic options for these patients. MDPI 2023-04-19 /pmc/articles/PMC10141691/ /pubmed/37108696 http://dx.doi.org/10.3390/ijms24087535 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Giner, Francisco
Machado, Isidro
Rubio-Martínez, Luis Alberto
López-Guerrero, José Antonio
Claramunt-Alonso, Reyes
Navarro, Samuel
Ferrández, Antonio
Mayordomo-Aranda, Empar
Llombart-Bosch, Antonio
Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling
title Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling
title_full Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling
title_fullStr Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling
title_full_unstemmed Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling
title_short Intimal Sarcoma with MDM2/CDK4 Amplification and p16 Overexpression: A Review of Histological Features in Primary Tumor and Xenograft, with Immunophenotype and Molecular Profiling
title_sort intimal sarcoma with mdm2/cdk4 amplification and p16 overexpression: a review of histological features in primary tumor and xenograft, with immunophenotype and molecular profiling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141691/
https://www.ncbi.nlm.nih.gov/pubmed/37108696
http://dx.doi.org/10.3390/ijms24087535
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