Title : Real-time molecular diagnosis of soft tissue tumors using water-assisted laser desorption/ionization mass spectrometry technology
A substantial number of lesions in soft tissue pathology requires diagnostic precision for adequate patient care management and follow-up. Also, margin status of surgical specimens must be unequivocally defined, preferably intra-operatively, because of the tight relation which exists between the quality of safe tumor margin delineation and remission. New discriminative diagnostic tools are needed to deal with these issues. Using canine tissues, we assessed the performance of a recently developed system, termed SpiderMass, relying on mass spectrometry (MS) for molecular lipid-based real-time diagnosis of sarcomas using endogenous water as matrix. SpiderMass uses a laser microprobe operating under ambient conditions and remotely fromrm the MS instrument with excitation of endogenous water molecules generating negligeable tissue destruction. 1-mm-thick sections obtained from 33 canine biopsies of various sarcoma subtypes such as fibrosarcoma, osteosarcoma and undifferentiated sarcoma were subjected to SpiderMass analysis. Results indicated that classification models based on moprhological criteria such as normal, cancerous and necrotic tissue , tumor grade, and subtypes showed a minimum of 97.63% correct classification using data collected with the system. Specific markers of normal, cancer, and necrotic regions were identified by tandem MS and validated by MS Imaging. SpiderMass differentiated grade 3 sarcomas from normal tissue and from grade 1 and 2 lesions and further subdivided specific tumor types with a high accuracy. Real-time detection capabilities were demonstrated by ex vivo analysis . We are currently focusing on applying the technique on human soft tissue tumors (maligant and benign) for a proof of concept with clinical samples aimed toward two novel developements : first, set up databases in the form of classification models of tumor sub-types and grades with their corresponding specific lipidomic profiles so as to construct histo-lipidomic classfications and, secondly, introduce in the instrumentation an artificial intellignence-type algorithmic bioinformatics system enabling it to rapidly consult, process and translate the databases into a point-of-care real-time diagnostic tool.