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Imagerie protéomique des neurinomes de l'acoustique et des nerfs normaux. Corrélations anatomopathologiques

Abstract : Objectives: Proteomic analysis of acoustic neuroma (AN), non-acoustic neuroma (NAN), and healthy nerve (hn) using the mass spectrometry and imaging of the MALDI-TOF (Matrix Assisted Laser Desorption Ionization-Time Of Flight).Materials and Methods: Prospective and qualitative study on AN, NAN, and hn. Samples were provided by the Bank of Tumor of the Pathology department of our institution, after signed consent from donor patients. Frozen samples were sectioned, analyzed histologically, then glued on a conductive slide and sprayed by an acid matrix. Thereafter, the laser beam of the MALDI performed desorption and then ionization of the sample. A mass spectrogram was drawn as a function of the time of flight of ionized protein biomolecules. Results has been transferred to a software to obtain a MALDI imaging with a color spectrum which depends on the protein content of the sample. The slide has been reexamined histologically and the results compared to those of the imaging.Results: Fifty neuromas have been sampled, of which 27 were exploitable. Eleven normal nerves were analyzed. Among the 22 analyzed AN, an almost total imaging-pathology correlation was seen in only 2 cases (9.1%), a partial correlation in 4 (18.2%), and no correlation in 16 (72.7%). The mass spectrogram showed a peptide spike at 2000 m/z in 7 cases (31.8%) and at 5000 m/z in all cases (100%). Among the 5 NAN, an almost total correlation was seen in 3 cases (60%), a partial correlation in 1 (20%), and no correlation in 1 (20%). The mass spectrogram showed a peptide spike at 2000 m/z in 2 cases (40%) and at 5000 m/z in 21 cases (95.5%). Among the 11 hn, an almost total correlation was seen in 9 cases (81.8%), a partial correlation in 1 (9.1%), and no correlation in 1 (9.1%).The mass spectrogram showed in no case a peptide spike at 2000 or at 5000 m/z. Behind homogeneous areas on histology, there was a great heterogeneity in MALDI imaging and on mass spectrometry, regarding AN and NAN, but not hn.Conclusions: the lack of correlation in acoustic neuroma could be due to its lack of growth and evolution compared to other neuromas and healthy nerves which presented a better correlation. The presence of two peptide spikes detected only in neuroma and not in healthy nerve opens up the prospect of tumor biomarkers and pathophysiological actors that should be purified and identified by sequencing. In the case of presence of an imaging-pathology correlation, histological areas of interest showed morphological aspects that were reproducible in the whole analyzed samples. This is the first work on proteomic imaging using the MALDI in acoustic neuroma and in neuromas in general. This is also a first comparison between proteomic imaging of the neuroma and that of normal nerve. Besides, and also for the first time, we found a proteomic polymorphism in acoustic neuroma and non-acoustic neuroma which were absent in normal nerve tissue thereby suggesting the presence de proteic biomarkers for the neuroma.
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Alexandre Karkas. Imagerie protéomique des neurinomes de l'acoustique et des nerfs normaux. Corrélations anatomopathologiques. Médecine humaine et pathologie. Université Grenoble Alpes, 2018. Français. ⟨NNT : 2018GREAS048⟩. ⟨tel-02628571⟩

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