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

Objective: The efficacy of anti-HER2 therapy is mainly dependent on HER2 overexpression in the metastatic lesions. It is essential to decipher the heterogeneity of gene profiles between primary tumor and matched metastases in gastric cancer.

Methods: The frequency of HER2 expression in 100 gastric cancers of both primary tumors and corresponding multiple lymph node metastases were determined immunohistochemically. A modified HER2-scoring criteria by Hofmann et al recommended for gastric cancer were followed in our study, which considers basolateral, so-called "U-shape", HER2-expression as positive.

Results: HER2 overexpression (2+, 3+) was seen in 33.0% of primary gastric cancers and 39.4% of the corresponding metastatic lymph nodes. For the first time, we compare HER2 expression heterogeneity among different lymph node metastases in the same patient, for the cases with 2 or more metastatic lymph nodes, HER2 expression discordance among the nodes was observed in 25.3% of the cases.

Conclusions: HER2 overexpression was seen in one-third of primary gastric cancers with lymph node metastases. As the receptor expression may lose or gain in the metastases at a probability of approximately 30%, assessment of the receptor status in metastatic lesions is encouraged.