10. Clinicopathological features of HER2 amplified pancreatic cancer

Background Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterised to define its clinical relevance and to exploit the potential of anti- HER2 therapies. Aims We aim to characterise the clinicopathological features of HER2 amplified pancreatic cancer. Our work extends the clinical relevance of our effect as part of the Australian Pancreatic Cancer Genome Initiative (APGI) in cataloguing genomic aberrations that characterise pancreatic cancer. Methods 469 cases of surgically resected pancreatic ductal adenocarcinoma (PDAC) from 12 institutions associated with the APGI from 1990 to 2012 were assessed for HER2 overexpression by immunohistochemistry and HER2 gene amplification by in situ hybridization. 55 of these cases were also assessed for DNA copy number changes and mRNA expression. Results HER2 amplification was found in 10 of 469 (2.1%) of samples. HER2 gene amplification was found in 100% (7/7) of HER2 3+, 11% (3/27) of HER2 2+ and none of 1+ overexpres-siong tumours. In all but one case, HER2 overexpression was uniform throughout tumours rather than showing clonal heterogeneity. HER2 amplification was associated with moderately differentiated tumours with distinctive macroglandular morphology. HER2 amplified tumours were also distinctive in their pattern of metastasis, with involvement of the lung ± brain without liver metastasis. Conclusions HER2 amplification occurs in 2% of PDAC and has distinct clinicopathological features with implications to clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti- HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification rather than organ of origin could make clinical trials of anti- HER2 therapies more feasible but needs to be well defined with robust diagnostic assays.