Research interests
Cancer is a very heterogeneous disease, making morphological classification and management of patients a significant challenge. Despite great advances it remains difficult to predict which patients are at risk of their disease returning (recurrence), spreading (metastasis) or which patients will gain most benefit to specific therapies. There has therefore been a concerted effort to supplement the morphological classification of disease with molecular parameters that can provide a clearer appreciation for this complexity and better predict tumour behaviour. This ideology has driven significant advancements in the field of molecular pathology research.
Peter's research program embraces these advances in technology to help better understand mechanisms of disease development and progression and help improve the molecular aspects of diagnosis and patient management. Themes of research involve 1) invasive lobular carcinoma of the breast, 2) familial breast cancer, and 3) lung cancer.
Invasive Lobular Carcinoma (ILC) is the most commonly diagnosed ‘special’ morphological type of breast cancer, comprising up to 15% of all cases. They exhibit a very characteristic set of clinical, pathological and biological properties, including a progressive decline in survival, an infiltrative pattern of growth and down regulation of cell adhesion molecule, E-cadherin. Morphological variants exist that are associated with a worse outcome compared to the classic type. A large component of Peter's research focuses on aspects of this specific disease subtype, including understanding molecular determinants that predict tumour behaviour, and mechanisms of invasion and metastasis.
Family history is a significant risk factor for the development of breast cancer. For some individuals and their families, the genetic component of this risk is well understood and attributed to pathogenic germline variants in moderate-high risk genes (e.g. BRCA1, BRCA2, PALB2, TP53, ATM, CHEK2). For most individuals the underlying genetic risk is unknown. We have been using whole genome sequencing of germline and matched tumour DNA to characterise somatic mutation signatures present in tumours from high risk individuals. These approaches are providing insight into the mechanisms driving tumourigenesis in familial breast cancers and also therapeutic strategies.
Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) sampling of lymph nodes is an important procedure to make a diagnosis of Lung cancer, particulalry in patients presenting with advanced, inoperable disease. Next generation sequencing is an important component of diagnostic practice and therapeutic decision making for lung cancer patients. Our program of work is focused on optimising sequencing approaches from small diagnostic aspirate samples yielded by EBUS TBNA.