MALDI mass spectrometry is able to acquire protein profiles directly from tissue that can describe the levels of hundreds of distinct proteins. MALDI imaging MS can simultaneously reveal how each of these proteins varies in heterogeneous tissues. Numerous studies have now demonstrated how MALDI imaging MS can generate different protein profiles from the different cell types in a tumor, which can act as biomarker profiles or enable specific candidate protein biomarkers to be identified. MALDI imaging MS can be directly applied to patient samples where its utility is to accomplish untargeted multiplex analysis of the tissue's protein content, enabling the different regions of the tissue to be differentiated on the basis of previously unknown protein profiles/biomarkers. The technique continues to rapidly develop and is now approaching the cusp whereby its potential to provide new diagnostic/prognostic tools for cancer patients can be routinely investigated. Here the latest methodological developments are summarized and its application to a range of tumors is reported in detail. The prospects of MALDI imaging MS are then described from the perspectives of modern pathological practice and MS-based proteomics, to ensure the outlook addresses real clinical needs and reflects the real capabilities of MS-based proteomics of complex tissue samples.
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