Comparison Of HER2Amplification And Overexpression In Primary Sites And Paired Metastatic Lymph Nodes Of Gastric Cancer

ObjectiveObserve the expression and gene status of HER-2in primary gastric cancer and metastastic lymph nodes. To investigate its association with clinicopathologic features, the relationship between HER-2overexpression and amplification, and the heterogeneity of HER-2overexpression and amplification between primary tumors and metastatic sites.MethodsThe HER-2status in gastric cancer (n=180) and metastastic lymph nodes(n=112) were detected by immunohistochemical(IHC) and fluorescence in-situ hybridization (FISH).The results were compared and its association with clinicopathologic features were analysed by SPSS17.0.ResultThe numbers of0,1+,2+and3+staining by IHC in180primary gastric cancer cases were139(77.2%),16(8.9%),15(8.3%) and10(5.6%); thus, HER-2expression positive rate of primary gastric cancers was13.9%; The numbers of0,1+,2+and3+staining by IHC in metastastic lymph nodes were80(71.5%),9(8.0%),14(12.5%) and9(8.0%) respectively; thus, the HER-2expression positive rate was20.5%. The difference between the two groups is not significant (P>0.05). Using FISH, none of the cases with1+by IHC shows HER-2gene amplification,11cases graded as2+by IHC and all3+staining cases shows HER-2amplification in primary gastric cancers; In contrast, in metastastic lymph nodes, none of the cases with1+by IHC shows HER-2gene amplification,10cases2+staining by IHC and all3+staining cases shows HER-2amplification. In the primary tumors and metastastic lymph nodes the concordance between HER2positivity by IHC and FISH was84.0%and82.6%respectively. There were6cases with discordant HER-2results between the primary tumor and corresponding lymph node metastasis.3were negative for HER-2overexpression and2were negative for HER-2amplification in primary lesions but showed positive conversion in metastastic lymph nodes, and no case showed negative conversion during the metastastic process. The positive rates of HER-2were significantly associated with clinical stage, Lauren type,lymph node metastasis, depth of invasion and the degree of differentiation (P<0.05)Conclusion:There was a high concordance between overexpression by IHC and amplification by FISH; The over-expression of HER-2is correlated to invasion, metastasis of gastric cancer. HER-2overexpression and amplification in metastatic sites have heterogeneity compared with primary tumors. HER-2status should be assessed also in the metastatic site further if HER-2is negative in primary tumors.