HER2 and EGFR status in pancreatic ductal adenocarcinomas (PDACs) and lymph node metastases

Abstract

4246 Background: The use of monoclonal antibody therapies against growth factor receptors as treatment for malignant tumours is on the increase. The potential usefulness of such therapies may be determined by assessment of the expression level of the receptor. Inter-study variation in the levels of the HER2 and EGFR receptors has been seen in PDACs. This study seeks to evaluate the expression rate of these receptors in metastatic PDACs, with regard to the possible use of monoclonal antibody therapies such as trastuzumab (Herceptin) in treating these tumours. Methods: 28 PDACs and their associated lymph node metastases underwent immunohistochemical staining for HER2 (CB11 antibody, Ventana) and EGFR (E30 antibody, Merck). HER2 gene amplification was also assessed by chromogenic in situ hybridisation (CISH, Zytomed). The percentage of cells in each sample that stained positive for HER2 was also analysed in a second series of 104 primaries only. Results: HER2 overexpression was seen in 28% of PDACs; 3+ overexpression was demonstrated in 10% of primary tumours and 21% of metastatic tumours. 28% of primary and metastatic tumours displayed HER2 gene amplification by CISH. EGFR was overexpressed in 50% of primaries and 28% of metastases. All lesions tumours classed as pancreatic intraepithelial neoplasia (PanIN, n=23) were negative for HER2 and EGFR, with the exception of three PanIN3 lesions that overexpressed HER2. 87% of samples had less than 50% of cells staining positive for HER2. Conclusions: The rate of HER2 overexpression in PDACs appears to be lower than previously reported. This suggests that these tumours are less suitable for treatment with HER2 antibody therapies such as trastuzumab. However, the high rate of EGFR overexpression indicates that this may be a promising therapeutic target in PDACs. No significant financial relationships to disclose.