Expressions Of Her2 And Her4 Isoforms And Their Significance In Pancreatic Ductal Adenocarcinoma

OBJECTIVE:To explore the proteins over-expression and gene status of HER2 and HER4, which are two members of epidermal growth factor receptor (EGFR) family, and to explore the relationship between those markers and pathologic features of pancreatic ductal adenocarcinoma (PDAC); To assess the correlation between HER2 and HER4 over-expression and gene status, and to investigate the role of copy number increase or amplification of HER2 and HER4 genes in the tumorigenesis, tumor size, differentiation degree, peripancreatic and liver metastasis and disease progression of PDAC.METHODS:We detected HER2 and HER4 protein expression by immunohisto-chemistry (IHC) method and gene amplification status by Fluorescence in Situ Hybridization (FISH) technique. We also analyzed the consistency between two methods and the relationship between protein expressions and gene amplification of HER2 and HER4 and tumor size, differentiation, metastasis and prognosis of PDAC.RESULTS:HER2 protein over expression and gene amplification rates were respectively 7.3%(4/55) and 9.1%(5/55). The rate of HER4 protein expression was 3.6%(2/55); we first detected the HER4 status at the genetic level in pancreatic cancer and found that the rate of HER4 amplification was only 3.6%(2/55). Statistical analysis showed that,1) the relationship between HER2 and HER4 with clinical pathological features of PDAC have not statistically significant (p>0.05); 2) HER2 protein expression and HER2 gene amplification have no correlation (p>0.05); 3) HER4 protein expression and HER4 gene amplification have no correlation either (p> 0.05); 4) The HER2 and HER4 protein expression was no correlation (r=0.05, p> 0.05);5) there was no significant correlation between HER2 and HER4 gene status either (r=0.06, p> 0.05).CONCLUSIONS:1) HER2 and HER4 in pancreatic ductal adenocarcinoma have a relatively low rate of protein expression and gene amplification rate; 2) HER2 and HER4 and clinical and pathological features have no relevance; 3) There are no correlation between protein expression and gene amplification of both HER2 and HER4, which is different from breast cancer.4) There is no sign of co-expression phenomenon of HER2 and HER4 in pancreatic cancer, which is different from the breast cancer or head and neck cancer either.5) Whether HER2 or HER4 could be considered as a potential drug target for treatment of pancreatic cancer remains to be unclear and should be further studied using more samples.