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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

Authors :
Francisco Giner
Isidro Machado
Luis Alberto Rubio-Martínez
José Antonio López-Guerrero
Reyes Claramunt-Alonso
Samuel Navarro
Antonio Ferrández
Empar Mayordomo-Aranda
Antonio Llombart-Bosch
Source :
International Journal of Molecular Sciences; Volume 24; Issue 8; Pages: 7535
Publication Year :
2023
Publisher :
Multidisciplinary Digital Publishing Institute, 2023.

Abstract

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.

Details

Language :
English
ISSN :
14220067
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences; Volume 24; Issue 8; Pages: 7535
Accession number :
edsair.doi.dedup.....6563686d7601da7f737a1d6ac294fa66
Full Text :
https://doi.org/10.3390/ijms24087535