HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies

Area of Science:

• Oncology
• Gastroenterology
• Molecular Diagnostics

Background:

• Human epidermal growth factor receptor-2 (HER2) is a validated therapeutic target in HER2-expressing gastro-oesophageal adenocarcinomas (GEA).
• Trastuzumab efficacy is well-established in HER2-positive GEA, necessitating accurate HER2 status assessment.

Purpose of the Study:

• To review current knowledge on HER2 status in dysplastic and neoplastic gastric conditions.
• To analyze methodologies for identifying HER2 expression/amplification and proposed scoring recommendations.
• To discuss the impact of HER2 expression heterogeneity on targeted therapy selection in GEA.

Main Methods:

• Literature review focusing on HER2 assessment in gastric conditions.
• Analysis of diagnostic procedures for HER2 expression and gene amplification.
• Evaluation of scoring systems and recommendations for HER2 evaluation.

Main Results:

• Significant heterogeneity in HER2 protein and gene expression exists in GEA, impacting targeted treatment selection.
• Current methodologies for HER2 assessment include immunohistochemistry and in situ hybridization.
• Standardized scoring recommendations are crucial for consistent HER2 evaluation.

Conclusions:

• Accurate HER2 assessment is critical for guiding trastuzumab therapy in GEA.
• Future biotechnological advancements will enhance HER2 detection systems.
• Liquid biopsy and analysis of additional gene mutations may predict HER2 resistance and monitor treatment response.