Molecular characterization of prostate cancer with associated Gleason score using mass spectrometry imaging.

Diagnosis of prostate cancer is based on histological evaluation of tumor architecture using a system known as the 'Gleason score'. This diagnostic paradigm, while the standard of care, is time-consuming, shows intra-observer variability 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 and progression. In this work, we present mass spectrometry imaging for identification and mapping of lipids and metabolites in 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 regions of tissue that appeared histologically benign, possibly suggestive of pre-cancerous metabolomic changes. A total of 31 lipids, including several phosphatidylcholines, phosphatidic acids, phosphatidylserines, phosphatidylinositols and cardiolipins were detected with higher intensity in GS (4+3) compared with GS (3+4), suggesting they may be markers of prostate cancer aggression. 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. Implications: In this study we suggest that metabolomic differences between prostate cancers with different Gleason scores can be detected by mass spectrometry imaging.