DIRECT PROFILING AND MALDI IMAGING OF TISSUES: NEW DEVELOPMENTS AND CLINICAL APPLICATIONS FOR OVARIAN CANCER
Résumé
MALDI direct analysis of tissues and imaging has shown to be a very powerful tool, it still require new developments. In peculiar, the search for new matrices that would be more adapted to direct tissue analysis was looked for. Ionic matrices were found to be especially well suited for such purpose. In peculiar, two matrices gave very good results for tissue analysis looking in term of crystallization, signal intensity, resolution, sensitivity and number of detected compounds compared to classical MALDI matrices. Moreover, in order to work on tissues kept in hospital libraries, FFPE tissues were studied. Fixation raises many problems for mass spectrometry analysis especially for long stored tissues. For older samples, no signal can be obtained directly from the tissues and a new strategy has to be developed. Thus, protocols of in situ tissue enzymatic digestion were developed. Using such a strategy in combination with automatic micro-spotting MALDI imaging of old tissues became possible. In addition, to increase the field of application of MALDI imaging, by giving access to other biomolecules than peptides/proteins, such as mRNA, or to lowly abundant, high mass or membrane proteins, a new concept of specific MALDI imaging was developed.. Using tagged oligonucleotide or antibody probes in combination with respectively In Situ Hybridization (ISH) or ImmunoCytoChemistry (ICC) will allow to performed molecular images of the repartition of specific mRNA or proteins by MALDI. All these new developments will be presented.