Elizabeth Randall, PhD: Molecular Characterization of Prostate Cancer and Gleason Score using Mass Spectrometry Imaging

Abstract

Prostate cancer is the most commonly diagnosed cancer in men in the US. Diagnosis of prostate cancer is based on histological evaluation of tumor architecture using a system known as the ‘Gleason score’ and Gleason grade grouping. This diagnostic paradigm, while the standard of care, is time-consuming, somewhat subjective, and provides no information about the altered metabolic pathways, which result in altered tissue architecture. Characterization of the molecular composition of prostate cancer and how it changes with respect to the Gleason score (GS) could enable a more objective and faster diagnosis. It may also aid in our understanding of disease onset, progression and possibly assist the identification of therapeutic targets. In this work, we present mass spectrometry imaging for identification and mapping of lipids and metabolites of prostate tissue from patients with known prostate cancer with GS from 6 to 9. A gradient of changes in the intensity of various lipids was observed, which correlated with increasing GS. Interestingly, these changes were identified in both regions of high tumor cell density, and in the tissue that appeared histologically benign. A total of 31 lipids, including phosphatidylcholines, phosphatidic acids, phosphatidylserines, phosphatidylinositols and cardiolipins were detected with higher intensity in GS (4+3) compared with GS (3+4) and may be markers of aggressive prostate cancer. Results obtained through mass spectrometry imaging studies were subsequently correlated with a fast, ambient mass spectrometry method for potential use as a clinical tool to support image-guided prostate biopsy.

Short Bio

Elizabeth graduated from the University of Birmingham in the UK in 2012 with a master’s degree in chemistry and went on to study Biomedical Imaging at Graduate School. Her PhD involved the development of multimodal chemical imaging methods for use in biomedical and pharmaceutical research. Elizabeth spent 2 years of her PhD undertaking research at the National Physical Laboratory in London, where she learned more about the fundamentals of measurement science and analytical chemistry. After completing her PhD in 2016, Elizabeth joined the lab of Dr. Nathalie Agar as an R25 fellow in partnership with the NCIGT at Brigham and Women’s Hospital. During this time she has been developing and applying various mass spectrometry based techniques to probe clinical and pre-clinical questions in cancer science, including the metabolism of prostate cancer, drug delivery and spatially resolved metabolism in brain tumors.