Clinical Significance Of HER2Expression In Primary And Lymph Node Metastatic Lesions Of Gastric Cancer

【Objective】To evaluate the level of HER2protein by immunohistochemistry (IHC) and expression of HER2gene amplification by fluorescence in situ hybridization (FISH) in prmary gastric cancer and metastastic lymph nodes. And to investigate the herterogeneous of HER2expression and its association with clinicopathologic features, comparision of HER2overexpression and amplification between primary and paired metastatic sites of gastric cancer.【Methods】1. The lever of HER2protein detected by EliVisionTM plus immunohistochemical in775gastric cancer surgical specimens and560metastatic lymph nodes lesions.2. The expression of HER2gene amplification was detected by FISH in71gastric cancer and paired lymph nodes sites.【Results】1. Of775gastric cancer specimens,132(17%) showed HER2protein overexpression by IHC (IHC2+and IHC3+); in the IHC2+and IHC3+cases, hetergeneous HER2protein expression ratio was75%(33/44),35.2%(31/88), respectively. HER2heterogeneity significantly associated with IHC2+(P＜0.05). Intratumoral heterogeneity had correlation with tumor differentiation and Lauren classification (P＜0.05), the cases with HER2heterogeneous expression tended to have the diffuse/mixed Lauren histological subtype, moderately and poorly differentiation, while not with sex, age, tumor site, depth of invasion, lymph node metastasis or distant metastasis (P＞0.05). Of560metastatic lymph nodes lesions, HER2protein overexpression ratio was18%(IHC2+and IHC3+), and the difference between metastasis and primary lesions was not significant (P＞0.05). Comparison of HER2status in560primary and paired metastatic lesions, there were41cases with discordant HER2results, and17cases showed HER2protein positive conversion;10cases showed negative conversion. 2. In primary gastric cancer lesions, the coincidence between HER2protein overexpression and gene amplification were IHC3+76.2%, IHC2+17.4%and IHC0/1+100%, respectively. While in metastatic lesions, the coincidence between HER2protein overexpression and gene amplification were IHC3+65.2%, IHC2+28.6%and IHC0/1+100%, respectively. Of all the41discordant cases,3cases analysed by FISH showed discordance between primary and metastatic lesions. All of them showed no HER2gene amplification in primary lesions, but showed HER2gene amplification in metastatic lesions (positive conversion); while negative conversion was not obsereved.【Conclusions】HER2expression had heterogeneity in gastric cancer. Heterogeneity was assicated with HER2protein weak expression. Intratumoral heterogeneity had correlation with tumor differentiation and Lauren classification. There was a good concordance between overexpression by IHC and gene amplification by FISH in HER2high expression and negative cases. The HER2status had a good overall concordance between metastatic and primary lesions, and HER2status was maintained in most cases unchanged during the metastatic process. While in the lymph node metastases, HER2status could occurre positive conversion or negative conversion, and if available, metastatic foci should do HER2testing.