Proteomic Imaging of Vestibular Schwannomas and Normal Nerves. Histopathologic Correlations.
Journal
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
ISSN: 1537-4505
Titre abrégé: Otol Neurotol
Pays: United States
ID NLM: 100961504
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
pubmed:
12
5
2021
medline:
8
10
2021
entrez:
11
5
2021
Statut:
ppublish
Résumé
Proteomic analysis of vestibular schwannoma (VS), non-vestibular schwannoma (NVS), and normal nerve (NN) using mass spectrometry and imaging of matrix assisted laser desorption ionization-time of flight (MALDI-TOF). Retrospective, qualitative, and descriptive study on VS, NVS, and NN. Samples were provided by our Tumor Bank. They were analyzed histologically then sprayed by acid matrix. The laser beam of MALDI performed desorption-ionization of the sample. A mass spectrogram (MS) was drawn depending on time of flight of ionized peptides, and MALDI-imaging was obtained which is a summation color spectrum depending on sample's peptide content. The slice was reexamined histologically and results compared with MALDI-imaging. Fifty schwannomas were sampled, of which 27 exploitable: 22 VS (17 Antoni type A and five type B) and five NVS (all Antoni type B). Eleven NN were analyzed. Among the 22 VS, near-total correlation between MALDI-imaging and pathology was found in two cases (9.1%), partial correlation in four (18.2%), and no correlation in 16 (72.7%); correlations were more frequent in VS of the Antoni type B. MS showed a peptide spike at 2,000 m/z in 7 (31.8%) and 5,000 m/z in 21 (95.5%). Among the five NVS, near-total correlation was found in three cases (60%), partial correlation in one (20%), and no correlation in one (20%). MS showed a peptide spike at 2,000 m/z in two (40%) and 5,000 m/z in all (100%). Among the 11 NN, near-total correlation was found in nine cases (81.8%), partial correlation in one (9.1%), and no correlation in one (9.1%). MS showed no peptide spike at 2,000 or 5,000 m/z. Behind homogeneous areas on histology, there was great heterogeneity on MALDI-imaging and MS, regarding VS and NVS, but not NN. There was a lack of correlation between MALDI-imaging and pathology in VS (except Antoni type B) as compared with NVS and NN. The lack of correlation in VS of the type A as compared with type B VS and NVS could be attributed to the overexpression of degeneration-associated proteins/peptides in VS of the type B as well as NVS that are better correlated with histologic findings. The two peptide spikes detected in schwannoma and not in NN opens up the prospect of tumor biomarkers identifiable by sequencing. The proteomic polymorphism found in VS and NVS was absent on histology which is a new morphologic characteristic of schwannoma. Further studies should be performed in the future to confirm the benefit and usefulness of the MALDI in the analysis of VS and NVS.
Identifiants
pubmed: 33973953
doi: 10.1097/MAO.0000000000003179
pii: 00129492-202109000-00041
doi:
Substances chimiques
Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1228-1236Informations de copyright
Copyright © 2021, Otology & Neurotology, Inc.
Déclaration de conflit d'intérêts
The authors disclose no conflicts of interest.
Références
Martianez T, Carrascal M, Lamarca A, et al. UTP affects the Schwannoma cell line proteome through P2Y receptors leading to cytoskeletal reorganisation. Proteomics 2012; 12:145–156.
Karkas A, Lamblin E, Meyer M, Gay E, Ternier J, Schmerber S. Trigeminal nerve deficit in large and compressive acoustic neuromas and its correlation with MRI findings. Otolaryngol Head Neck Surg 2014; 151:675–680.
Welling DBPM, Akhmametyeva EM, Chang LS. Bambakidis NC, Megerian CA, Spetzler RE. Biology and genetics of vestibular schwannomas in tumors of the cerebellopontine angle. Surgery of the Cerebellopontine Angle . Hamilton, Ontario, Canada: BC Decker; 2009. 119–134.
Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature 2003; 422:198–207.
Seo JH, Park KH, Jeon EJ, et al. Proteomic analysis of vestibular schwannoma: conflicting role of apoptosis on the pathophysiology of sporadic vestibular schwannoma. Otol Neurotol 2015; 36:714–719.
Addie RD, Balluff B, Bovee JV, Morreau H, McDonnell LA. Current state and future challenges of mass spectrometry imaging for clinical research. Anal Chem 2015; 87:6426–6433.
Kazemizadeh Gol MA, Lund TC, Levine SC, Adams ME. Quantitative proteomics of vestibular schwannoma cerebrospinal fluid: a pilot study. Otolaryngol Head Neck Surg 2016; 154:902–906.
Ait-Belkacem R, Berenguer C, Villard C, et al. MALDI imaging and in-source decay for top-down characterization of glioblastoma. Proteomics 2014; 14:1290–1301.
Abe M, Kawase T, Urano M, et al. Analyses of proliferative potential in schwannomas. Brain Tumor Pathol 2000; 17:35–40.
Diologent L, Franck J, Wisztorski M, et al. On the origin of increased sensitivity and mass resolution using silicon masks in MALDI. Anal Chem 2014; 86:1404–1413.
Bassiri K, Ferluga S, Sharma V, et al. Global proteome and phospho-proteome analysis of Merlin-deficient meningioma and schwannoma identifies PDLIM2 as a novel therapeutic target. EBioMedicine 2017; 16:76–86.
Caprioli RM, Farmer TB, Gile J. Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 1997; 69:4751–4760.
Hardesty WM, Kelley MC, Mi D, Low RL, Caprioli RM. Protein signatures for survival and recurrence in metastatic melanoma. J Proteomics 2011; 74:1002–1014.
Almendro V, Marusyk A, Polyak K. Cellular heterogeneity and molecular evolution in cancer. Annu Rev Pathol 2013; 8:277–302.
McGranahan N, Swanton C. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell 2015; 27:15–26.
McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 2017; 168:613–628.
Caye-Thomasen P, Baandrup L, Jacobsen GK, Thomsen J, Stangerup SE. Immunohistochemical demonstration of vascular endothelial growth factor in vestibular schwannomas correlates to tumor growth rate. Laryngoscope 2003; 113:2129–2134.
Koutsimpelas D, Stripf T, Heinrich UR, Mann WJ, Brieger J. Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics. Otol Neurotol 2007; 28:1094–1099.
Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med 2009; 361:358–367.
Wong HK, Lahdenranta J, Kamoun WS, et al. Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. Cancer Res 2010; 70:3483–3493.
Altuna X, Lopez JP, Yu MA, et al. Potential role of imatinib mesylate (Gleevec, STI-571) in the treatment of vestibular schwannoma. Otol Neurotol 2011; 32:163–170.
Schmucker B, Ballhausen WG, Kressel M. Subcellular localization and expression pattern of the neurofibromatosis type 2 protein merlin/schwannomin. Eur J Cell Biol 1997; 72:46–53.