HER2 expression variability between primary gastric cancers and corresponding lymph node metastases

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Anti-HER2 therapy efficacy relies on HER2 overexpression in metastatic sites.
• Gastric cancer exhibits significant gene profile heterogeneity between primary tumors and metastases.
• Understanding this heterogeneity is crucial for personalized treatment strategies.

Purpose of the Study:

• To investigate the heterogeneity of HER2 expression between primary gastric tumors and matched lymph node metastases.
• To determine the frequency of HER2 overexpression in gastric cancer and its metastatic lymph nodes.
• To assess discordance in HER2 expression among multiple lymph node metastases within the same patient.

Main Methods:

• Immunohistochemistry was used to determine HER2 expression frequency in 100 primary gastric cancers and their corresponding lymph node metastases.
• A modified HER2-scoring criteria, including basolateral 'U-shape' expression, was applied as recommended for gastric cancer.
• HER2 expression heterogeneity was analyzed among different lymph node metastases in patients with multiple positive nodes.

Main Results:

• HER2 overexpression (2+, 3+) was observed in 33.0% of primary gastric cancers and 39.4% of metastatic lymph nodes.
• HER2 expression discordance among lymph node metastases was found in 25.3% of cases with two or more positive nodes.
• This study provides the first comparison of HER2 expression heterogeneity across different lymph node metastases in the same gastric cancer patient.

Conclusions:

• Approximately one-third of primary gastric cancers with lymph node metastases show HER2 overexpression.
• HER2 receptor status can be gained or lost in metastases with approximately 30% probability.
• Assessing HER2 receptor status in metastatic lesions is recommended to guide anti-HER2 therapy decisions.