HER2 gene amplification and protein expression in pancreatic ductal adenocarcinomas.

BACKGROUND

Despite advances in combination therapies, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Blocking of overexpressed HER2 oncogene improves survival in breast and gastroesophageal cancer and might be also a therapeutic option in PDAC. The purpose of this study was to evaluate HER2 gene amplification and protein expression in PDAC.

METHODS

HER2 protein expression was investigated using a FDA-approved antibody in 87 formalin-fixed and paraffin-embedded cases of PDAC with complete follow-up. HER2 gene amplification was assessed on tissue microarrays using dual color silver in situ hybridization (DISH).

RESULTS

Generally, HER2 immunostaining showed considerable heterogeneity. In 19 cases, ≥10 of tumor cells showed some positive reaction. In no case, complete membranous staining was observed. Using the scoring system developed for assessment of HER2 status in gastroesophageal cancer, 9 cases showed positive immunohistologic staining (score 2+ to 3+). After performing DISH, 6 (7%) immunohistochemically 2+ or 3+ cases were found to have HER2 gene amplification, whereas none of these cases showed polyploidy. No association of HER2 status and clinicopathologic parameters or survival was observed (P>0.05).

CONCLUSIONS

HER2 is overexpressed in a subset of PDACs, identifying them as possible candidates for a targeted therapy. For assessment of HER2 status in PDAC, the scoring system originally developed for gastric cancer is recommend.