RESUMO
BACKGROUND: Liposarcomas are among the most common mesenchymal malignancies. However, the therapeutic options are still very limited and so far, targeted therapies had not yet been established. Immunotherapy, which has been a breakthrough in other oncological entities, seems to have no efficacy in liposarcoma. Complicating matters further, classification remains difficult due to the diversity of morphologies and nonspecific or absent markers in immunohistochemistry, leaving molecular pathology using FISH or sequencing as best options. Many liposarcomas harbor MDM2 gene amplifications. In close relation to the gene locus of MDM2, HER3 (ERBB3) gene is present and co-amplification could occur. Since the group of HER/EGFR receptor tyrosine kinases and its inhibitors/antibodies play a role in a broad spectrum of oncological diseases and treatments, and some HER3 inhibitors/antibodies are already under clinical investigation, we hypothesized that in case of HER3 co-amplifications a tumor might bear a further potential therapeutic target. METHODS: We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma. RESULTS: Next to 16 out of 56 cases needed to be re-classified, in 20 out of 54 cases, a cluster-amplification of HER3 could be detected, significantly correlating with MDM2 amplification. Our study shows that the entity of liposarcomas show specific molecular characteristics leading to reclassify archived cases by modern, established methodologies. Additionally, in 57.1% of these cases, HER3 was cluster-amplified profusely, presenting a putative therapeutic target for targeted therapy. CONCLUSION: Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.
Assuntos
Amplificação de Genes , Lipossarcoma , Proteínas Proto-Oncogênicas c-mdm2 , Receptor ErbB-3 , Humanos , Lipossarcoma/genética , Lipossarcoma/patologia , Lipossarcoma/metabolismo , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Hibridização in Situ Fluorescente , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Masculino , Prognóstico , Pessoa de Meia-Idade , Idoso , Terapia de Alvo Molecular/métodos , AdultoRESUMO
The recent advance in hybrid imaging techniques enables offering simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) in various clinical fields. 18F-fluorodeoxyglucose (FDG) PET has been widely used for diagnosis and evaluation of oncologic patients. The growing evidence from research and clinical experiences demonstrated that PET/MRI with FDG can provide comparable or superior diagnostic performance more than conventional radiological imaging such as computed tomography (CT), MRI or PET/CT in various cancers. Combined analysis using structural information and functional/molecular information of tumors can draw additional diagnostic information based on PET/MRI. Further studies including determination of the diagnostic efficacy, optimizing the examination protocol, and analysis of the hybrid imaging results is necessary for extending the FDG PET/MRI application in clinical oncology.
