# HER3 (ERBB3) amplification in liposarcoma - a putative new therapeutic target?

## TL;DR

This study explores HER3 gene amplification in liposarcoma, suggesting it could be a new target for targeted therapies.

## Contribution

The study identifies HER3 co-amplification with MDM2 in liposarcoma, proposing it as a novel therapeutic target.

## Key findings

- HER3 gene cluster amplification was detected in 57.1% of liposarcoma cases.
- HER3 amplification significantly correlates with MDM2 amplification in these tumors.

## Abstract

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.