HER3 (ERBB3) amplification in liposarcoma - a putative new therapeutic target?
Coamplification
DDIT3
ERBB3
Fluoresence in situ hybridization (FISH) immunohistochemistry
HER3
Liposarcoma
MDM2 amplification
Journal
World journal of surgical oncology
ISSN: 1477-7819
Titre abrégé: World J Surg Oncol
Pays: England
ID NLM: 101170544
Informations de publication
Date de publication:
17 May 2024
17 May 2024
Historique:
received:
29
02
2024
accepted:
07
05
2024
medline:
18
5
2024
pubmed:
18
5
2024
entrez:
17
5
2024
Statut:
epublish
Résumé
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. We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma. 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. Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.
Sections du résumé
BACKGROUND
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
METHODS
We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma.
RESULTS
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
CONCLUSIONS
Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.
Identifiants
pubmed: 38760830
doi: 10.1186/s12957-024-03406-5
pii: 10.1186/s12957-024-03406-5
doi:
Substances chimiques
ERBB3 protein, human
0
MDM2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
131Informations de copyright
© 2024. The Author(s).
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