Evaluation and validation of MALDI-IMS in molecular pathology

• Applicant: Professor Dr. Christoph Röcken
• Co-Applicants: Professor Holger Kalthoff, Ph.D.; Professor Dr. Jens-Michael Schröder; Professor Dr. Andreas Tholey
• Subject Area: Hematology, Oncology
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 207585601

Matrix-assisted laser desorption ionization-based imaging mass spectrometry (MALDI-IMS) is a relatively new and effective tool for the molecular analysis of complex biological samples such as tissue sections. It has demonstrated its applicability and potential on small patient and tissue sample series. However, vali-dation of its robustness and potential for personalized medicine on large patient series is still missing. This collaborative initiative of four interactive and highly interdisciplinary research groups with a specific background knowledge and expertise on mass spectrometry aims to exploit and apply novel ionic (liquid) matrices for MALDI-IMS, validate the diagnostic, prognostic and predictive capability of MALDI-IMS on four large patient series [gastric cancer (544 patients), colon cancer (>1500 patients), pancreatic cancer (>200 patients) and amyloidosis (>1500 patients)], and to understand the topospecific localization of mi-crobes, its products and its interaction with epithelial host defense molecules in healthy as well as in-flamed skin. With regard to oncology and amyloidosis we wish to test the following hypotheses and trans-lational aspects: MALDI-IMS as a single technology is able to provide the same amount of information from tissue samples like the combination of three separate techniques together, i.e. histology, immunohis-tochemistry and molecular biology; MALDI-IMS provides biomarker sets that are able to provide superior prognostic information compared with “conventional“ histological classification of human tumors; MALDI-IMS can be used to predict treatment response; MALDI-IMS facilitates the diagnosis and classification of amyloid; MALDI-IMS facilitates monitoring of therapy response. With regard to mucosal integrity we wish to test the hypotheses that indigenous skin microorganisms provide some benefit to the host by producing pathogen-killing antimicrobial compounds in a topospecific manner. Biomarker identification and valida-tion will be an integral part of these projects.

• DFG Programme: Major Instrumentation Initiatives
• Major Instrumentation: MALDI TOF/TOF
• Instrumentation Group: 1700 Massenspektrometer