Developing diagnostic methods for challenging pancreatobiliary tumours

This study will involve a combination of bioinformatic and basic histology and/or molecular methods.

Places available:

  • One Honours

Defined by the absence of confirmed cancer type diagnosis  cancer of unknown primary (CUP) is a devastating disease with an exceptionally poor outcome. Developing better diagnostic methods is therefore important to direct optimal therapy.

Gene-expression and mutational profiling has been used by our laboratory to develop tissue of origin diagnostic tests that can help resolve the origin of CUP tumours. These tests can have an accuracy of approximately 80-85% across major known cancer types. However, one group of tumours that can still be challenging to classify are pancreatobilary tumours including intrahepatic and extrahepatic cholangiocarcinomas, pancreatic ductal adenocarcinomas and tumours of the ampulla. Indeed, the distinction between adenocarcinomas of the pancreas, bile duct, kidney and other sites are known diagnostic dilemmas for anatomical pathologists, where immunohistochemistry can be of limited value but where an accurate diagnosis is critical, as treatment can be very different based on the cancer type. The identification of biomarkers or molecular methods that can help resolve these tumours is therefore required.

This project will involve a combination of bioinformatic and basic histology and/or molecular methods. Published and locally generated gene-expression and mutation datasets will be collated representing hepatocellular carcinomas, bile duct cancers (intra and extra-hepatic cholangiocarcinoma), other adenocarcinomas as well as CUPs suspected of being pancreatobiliary tumours. Gene sets that can distinguish between pancreatobillary tumours  and other cancer types will be identified and machine learning will then be employed to develop a classifier. Individual genes will also be surveyed to identify putative immunohistochemistry (protein) or in situ hybridisation (RNA) targets that can be used by anatomical pathologists in a routine histopathology setting.

Contact and more information

Associate Professor Richard Tothill