Progress and Potential of Imaging Mass Spectrometry Applied to Biomarker Discovery

  • Jusal Quanico
  • Julien Franck
  • Maxence Wisztorski
  • Michel Salzet
  • Isabelle FournierEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1598)


Mapping provides a direct means to assess the impact of protein biomarkers and puts into context their relevance in the type of cancer being examined. To this end, mass spectrometry imaging (MSI) was developed to provide the needed spatial information which is missing in traditional liquid-based mass spectrometric proteomics approaches. Aptly described as a “molecular histology” technique, MSI gives an additional dimension in characterizing tumor biopsies, allowing for mapping of hundreds of molecules in a single analysis. A decade of developments focused on improving and standardizing MSI so that the technique can be translated into the clinical setting. This review describes the progress made in addressing the technological development that allows to bridge local protein detection by MSI to its identification and to illustrate its potential in studying various aspects of cancer biomarker discovery.

Key words

Mass spectrometry imaging Molecular histology Biomarker Protein identification Microextraction Matrix-assisted laser desorption/ionization 


  1. 1.
    Kallback P, Shariatgorji M, Nilsson A, Andren PE (2012) Novel mass spectrometry imaging software assisting labeled normalization and quantitation of drugs and neuropeptides directly in tissue sections. J Proteomics 75:4941–4951CrossRefPubMedGoogle Scholar
  2. 2.
    Hamm G, Bonnel D, Legouffe R, Pamelard F, Delbos JM, Bouzom F, Stauber J (2012) Quantitative mass spectrometry imaging of propranolol and olanzapine using tissue extinction calculation as normalization factor. J Proteomics 75:4952–4961CrossRefPubMedGoogle Scholar
  3. 3.
    Takai N, Tanaka Y, Watanabe A, Saji H (2013) Quantitative imaging of a therapeutic peptide in biological tissue sections by MALDI MS. Bioanalysis 5:603–612CrossRefPubMedGoogle Scholar
  4. 4.
    Shanta SR, Kim TY, Hong JH, Lee JH, Shin CY, Kim KH, Kim YH, Kim SK, Kim KP (2012) A new combination MALDI matrix for small molecule analysis: application to imaging mass spectrometry for drugs and metabolites. Analyst 137:5757–5762CrossRefPubMedGoogle Scholar
  5. 5.
    Bhandari DR, Schott M, Rompp A, Vilcinskas A, Spengler B (2015) Metabolite localization by atmospheric pressure high-resolution scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging in whole-body sections and individual organs of the rove beetle Paederus riparius. Anal Bioanal Chem 407:2189–2201CrossRefPubMedGoogle Scholar
  6. 6.
    Li B, Bhandari DR, Janfelt C, Rompp A, Spengler B (2014) Natural products in Glycyrrhiza glabra (licorice) rhizome imaged at the cellular level by atmospheric pressure matrix-assisted laser desorption/ionization tandem mass spectrometry imaging. Plant J 80:161–171CrossRefPubMedGoogle Scholar
  7. 7.
    Demeyer M, Wisztorski M, Decroo C, De Winter J, Caulier G, Hennebert E, Eeckhaut I, Fournier I, Flammang P, Gerbaux P (2015) Inter- and intra-organ spatial distributions of sea star saponins by MALDI imaging. Anal Bioanal Chem 407:8813–8824CrossRefPubMedGoogle Scholar
  8. 8.
    Sturtevant D, Lee YJ, Chapman KD (2016) Matrix assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) for direct visualization of plant metabolites in situ. Curr Opin Biotechnol 37:53–60CrossRefPubMedGoogle Scholar
  9. 9.
    Cerruti CD, Benabdellah F, Laprevote O, Touboul D, Brunelle A (2012) MALDI imaging and structural analysis of rat brain lipid negative ions with 9-aminoacridine matrix. Anal Chem 84:2164–2171CrossRefPubMedGoogle Scholar
  10. 10.
    Ruh H, Salonikios T, Fuchser J, Schwartz M, Sticht C, Hochheim C, Wirnitzer B, Gretz N, Hopf C (2013) MALDI imaging MS reveals candidate lipid markers of polycystic kidney disease. J Lipid Res 54:2785–2794CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Veselkov KA, Mirnezami R, Strittmatter N, Goldin RD, Kinross J, Speller AV, Abramov T, Jones EA, Darzi A, Holmes E, Nicholson JK, Takats Z (2014) Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer. Proc Natl Acad Sci U S A 111:1216–1221CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mitchell CA, Long H, Donaldson M, Francese S, Clench MR (2015) Lipid changes within the epidermis of living skin equivalents observed across a time-course by MALDI-MS imaging and profiling. Lipids Health Dis 14:84CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gustafsson OJ, Briggs MT, Condina MR, Winderbaum LJ, Pelzing M, McColl SR, Everest-Dass AV, Packer NH, Hoffmann P (2015) MALDI imaging mass spectrometry of N-linked glycans on formalin-fixed paraffin-embedded murine kidney. Anal Bioanal Chem 407:2127–2139CrossRefPubMedGoogle Scholar
  14. 14.
    Powers TW, Neely BA, Shao Y, Tang H, Troyer DA, Mehta AS, Haab BB, Drake RR (2014) MALDI imaging mass spectrometry profiling of N-glycans in formalin-fixed paraffin embedded clinical tissue blocks and tissue microarrays. PLoS One 9:e106255CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Toghi Eshghi S, Yang S, Wang X, Shah P, Li X, Zhang H (2014) Imaging of N-linked glycans from formalin-fixed paraffin-embedded tissue sections using MALDI mass spectrometry. ACS Chem Biol 9:2149–2156CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Powers TW, Holst S, Wuhrer M, Mehta AS, Drake RR (2015) Two-dimensional N-glycan distribution mapping of hepatocellular carcinoma tissues by MALDI-imaging mass spectrometry. Biomolecules 5:2554–2572CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Briggs MT, Kuliwaba JS, Muratovic D, Everest-Dass AV, Packer NH, Findlay DM, Hoffmann P (2016) MALDI mass spectrometry imaging of N-glycans on tibial cartilage and subchondral bone proteins in knee osteoarthritis. Proteomics, published online 15 Mar 2016, doi:0 10.1002/pmic.201500461
  18. 18.
    Pratavieira M, da Silva Menegasso AR, Garcia AM, Dos Santos DS, Gomes PC, Malaspina O, Palma MS (2014) MALDI imaging analysis of neuropeptides in the Africanized honeybee (Apis mellifera) brain: effect of ontogeny. J Proteome Res 13:3054–3064CrossRefPubMedGoogle Scholar
  19. 19.
    Jiao J, Miao A, Zhang Y, Fan Q, Lu Y, Lu H (2015) Imaging phosphorylated peptide distribution in human lens by MALDI MS. Analyst 140:4284–4290CrossRefPubMedGoogle Scholar
  20. 20.
    OuYang C, Chen B, Li L (2015) High throughput in situ DDA analysis of neuropeptides by coupling novel multiplex mass spectrometric imaging (MSI) with gas-phase fractionation. J Am Soc Mass Spectrom 26:1992–2001CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Klein O, Strohschein K, Nebrich G, Oetjen J, Trede D, Thiele H, Alexandrov T, Giavalisco P, Duda GN, von Roth P, Geissler S, Klose J, Winkler T (2014) MALDI imaging mass spectrometry: discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures. Proteomics 14:2249–2260CrossRefPubMedGoogle Scholar
  22. 22.
    Hunt NJ, Phillips L, Waters KA, Machaalani R (2016) Proteomic MALDI-TOF/TOF-IMS examination of peptide expression in the formalin fixed brainstem and changes in sudden infant death syndrome infants. J Proteomics 138:48–60CrossRefPubMedGoogle Scholar
  23. 23.
    Schey KL, Hachey AJ, Rose KM, Grey AC (2016) MALDI imaging mass spectrometry of pacific white shrimp L. vannamei and identification of abdominal muscle proteins. Proteomics, published online 16 Mar 2016, doi: 10.1002/pmic.201500531
  24. 24.
    Spraggins JM, Rizzo DG, Moore JL, Noto MJ, Skaar EP, Caprioli RM (2016) Next-generation technologies for spatial proteomics: integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis. Proteomics, published online 6 Apr 2016, doi: 10.1002/pmic.201600003
  25. 25.
    Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69:4751–4760CrossRefPubMedGoogle Scholar
  26. 26.
    Cillero-Pastor B, Heeren RM (2014) Matrix-assisted laser desorption ionization mass spectrometry imaging for peptide and protein analyses: a critical review of on-tissue digestion. J Proteome Res 13:325–335CrossRefPubMedGoogle Scholar
  27. 27.
    Chaurand P (2012) Imaging mass spectrometry of thin tissue sections: a decade of collective efforts. J Proteomics 75:4883–4892CrossRefPubMedGoogle Scholar
  28. 28.
    Goodwin RJ (2012) Sample preparation for mass spectrometry imaging: small mistakes can lead to big consequences. J Proteomics 75:4893–4911CrossRefPubMedGoogle Scholar
  29. 29.
    Shimma S, Sugiura Y (2014) Effective sample preparations in imaging mass spectrometry. Mass Spectrom 3:S0029CrossRefGoogle Scholar
  30. 30.
    Thomas A, Chaurand P (2014) Advances in tissue section preparation for MALDI imaging MS. Bioanalysis 6:967–982CrossRefPubMedGoogle Scholar
  31. 31.
    Jungmann JH, Heeren RM (2012) Emerging technologies in mass spectrometry imaging. J Proteomics 75:5077–5092CrossRefPubMedGoogle Scholar
  32. 32.
    Gessel MM, Norris JL, Caprioli RM (2014) MALDI imaging mass spectrometry: spatial molecular analysis to enable a new age of discovery. J Proteomics 107:71–82CrossRefPubMedGoogle Scholar
  33. 33.
    Trim PJ, Djidja MC, Muharib T, Cole LM, Flinders B, Carolan VA, Francese S, Clench MR (2012) Instrumentation and software for mass spectrometry imaging—making the most of what you've got. J Proteomics 75:4931–4940CrossRefPubMedGoogle Scholar
  34. 34.
    Jones EA, Deininger SO, Hogendoorn PC, Deelder AM, McDonnell LA (2012) Imaging mass spectrometry statistical analysis. J Proteomics 75:4962–4989CrossRefPubMedGoogle Scholar
  35. 35.
    Alexandrov T (2012) MALDI imaging mass spectrometry: statistical data analysis and current computational challenges. BMC Bioinformatics 13(Suppl 16):S11PubMedPubMedCentralGoogle Scholar
  36. 36.
    Trede D, Kobarg JH, Oetjen J, Thiele H, Maass P, Alexandrov T (2012) On the importance of mathematical methods for analysis of MALDI-imaging mass spectrometry data. J Integr Bioinform 9:189PubMedGoogle Scholar
  37. 37.
    Aichler M, Walch A (2015) MALDI Imaging mass spectrometry: current frontiers and perspectives in pathology research and practice. Lab Invest 95:422–431CrossRefPubMedGoogle Scholar
  38. 38.
    Minerva L, Ceulemans A, Baggerman G, Arckens L (2012) MALDI MS imaging as a tool for biomarker discovery: methodological challenges in a clinical setting. Proteomics Clin Appl 6:581–595CrossRefPubMedGoogle Scholar
  39. 39.
    Schwamborn K (2012) Imaging mass spectrometry in biomarker discovery and validation. J Proteomics 75:4990–4998CrossRefPubMedGoogle Scholar
  40. 40.
    Kriegsmann J, Kriegsmann M, Casadonte R (2015) MALDI TOF imaging mass spectrometry in clinical pathology: a valuable tool for cancer diagnostics (review). Int J Oncol 46:893–906PubMedGoogle Scholar
  41. 41.
    Schone C, Hofler H, Walch A (2013) MALDI imaging mass spectrometry in cancer research: combining proteomic profiling and histological evaluation. Clin Biochem 46:539–545CrossRefPubMedGoogle Scholar
  42. 42.
    Lanni EJ, Rubakhin SS, Sweedler JV (2012) Mass spectrometry imaging and profiling of single cells. J Proteomics 75:5036–5051CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Franck J, Arafah K, Barnes A, Wisztorski M, Salzet M, Fournier I (2009) Improving tissue preparation for matrix-assisted laser desorption ionization mass spectrometry imaging. Part 1: Using microspotting. Anal Chem 81:8193–8202CrossRefPubMedGoogle Scholar
  44. 44.
    van de Ven S, Bemis KD, Lau K, Adusumilli R, Kota U, Stolowitz M, Vitek O, Mallick P, Gambhir SS (2016) Protein biomarkers on tissue as imaged via MALDI mass spectrometry: a systematic approach to study the limits of detection. Proteomics, published online 11 Mar 2016, doi: 10.1002/pmic.201500515
  45. 45.
    Yang J, Caprioli RM (2011) Matrix sublimation/recrystallization for imaging proteins by mass spectrometry at high spatial resolution. Anal Chem 83:5728–5734CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Bouschen W, Schulz O, Eikel D, Spengler B (2010) Matrix vapor deposition/recrystallization and dedicated spray preparation for high-resolution scanning microprobe matrix-assisted laser desorption/ionization imaging mass spectrometry (SMALDI-MS) of tissue and single cells. Rapid Commun Mass Spectrom 24:355–364CrossRefPubMedGoogle Scholar
  47. 47.
    Yang J, Caprioli RM (2014) Matrix pre-coated targets for high throughput MALDI imaging of proteins. J Mass Spectrom 49:417–422CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Wang X, Han J, Hardie DB, Yang J, Borchers CH (2016) The use of matrix coating assisted by an electric field (MCAEF) to enhance mass spectrometric imaging of human prostate cancer biomarkers. J Mass Spectrom 51:86–95CrossRefPubMedGoogle Scholar
  49. 49.
    Lemaire R, Wisztorski M, Desmons A, Tabet JC, Day R, Salzet M, Fournier I (2006) MALDI-MS direct tissue analysis of proteins: improving signal sensitivity using organic treatments. Anal Chem 78:7145–7153CrossRefPubMedGoogle Scholar
  50. 50.
    Grey AC, Chaurand P, Caprioli RM, Schey KL (2009) MALDI imaging mass spectrometry of integral membrane proteins from ocular lens and retinal tissue. J Proteome Res 8:3278–3283CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Franck J, Longuespee R, Wisztorski M, Van Remoortere A, Van Zeijl R, Deelder A, Salzet M, McDonnell L, Fournier I (2010) MALDI mass spectrometry imaging of proteins exceeding 30,000 daltons. Med Sci Monit 16:BR293–BR299PubMedGoogle Scholar
  52. 52.
    Stauber J, Ayed ME, Wisztorski M, Salzet M, Fournier I (2010) Specific MALDI-MSI: Tag-Mass. Methods Mol Biol 656:339–361CrossRefPubMedGoogle Scholar
  53. 53.
    Lemaire R, Menguellet SA, Stauber J, Marchaudon V, Lucot JP, Collinet P, Farine MO, Vinatier D, Day R, Ducoroy P, Salzet M, Fournier I (2007) Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker. J Proteome Res 6:4127–4134CrossRefPubMedGoogle Scholar
  54. 54.
    Liu R, Li Q, Smith LM (2014) Detection of large ions in time-of-flight mass spectrometry: effects of ion mass and acceleration voltage on microchannel plate detector response. J Am Soc Mass Spectrom 25:1374–1383CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    van Remoortere A, van Zeijl RJ, van den Oever N, Franck J, Longuespee R, Wisztorski M, Salzet M, Deelder AM, Fournier I, McDonnell LA (2010) MALDI imaging and profiling MS of higher mass proteins from tissue. J Am Soc Mass Spectrom 21:1922–1929PubMedGoogle Scholar
  56. 56.
    Ellis SR, Jungmann JH, Smith DF, Soltwisch J, Heeren RM (2013) Enhanced detection of high-mass proteins by using an active pixel detector. Angew Chem Int Ed Engl 52:11261–11264CrossRefPubMedGoogle Scholar
  57. 57.
    Jungmann JH, Heeren RM (2013) Detection systems for mass spectrometry imaging: a perspective on novel developments with a focus on active pixel detectors. Rapid Commun Mass Spectrom 27:1–23CrossRefPubMedGoogle Scholar
  58. 58.
    Li J, Inutan ED, Wang B, Lietz CB, Green DR, Manly CD, Richards AL, Marshall DD, Lingenfelter S, Ren Y, Trimpin S (2012) Matrix assisted ionization: new aromatic and nonaromatic matrix compounds producing multiply charged lipid, peptide, and protein ions in the positive and negative mode observed directly from surfaces. J Am Soc Mass Spectrom 23:1625–1643CrossRefPubMedGoogle Scholar
  59. 59.
    Debois D, Smargiasso N, Demeure K, Asakawa D, Zimmerman TA, Quinton L, De Pauw E (2013) MALDI in-source decay, from sequencing to imaging. Top Curr Chem 331:117–141CrossRefPubMedGoogle Scholar
  60. 60.
    Asakawa D, Calligaris D, Zimmerman TA, De Pauw E (2013) In-source decay during matrix-assisted laser desorption/ionization combined with the collisional process in an FTICR mass spectrometer. Anal Chem 85:7809–7817CrossRefPubMedGoogle Scholar
  61. 61.
    Syka JE, Coon JJ, Schroeder MJ, Shabanowitz J, Hunt DF (2004) Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci U S A 101:9528–9533CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Inutan ED, Richards AL, Wager-Miller J, Mackie K, McEwen CN, Trimpin S (2011) Laserspray ionization, a new method for protein analysis directly from tissue at atmospheric pressure with ultrahigh mass resolution and electron transfer dissociation. Mol Cell Proteomics 10:M110 000760CrossRefPubMedGoogle Scholar
  63. 63.
    Spraggins JM, Rizzo DG, Moore JL, Rose KL, Hammer ND, Skaar EP, Caprioli RM (2015) MALDI FTICR IMS of intact proteins: using mass accuracy to link protein images with proteomics data. J Am Soc Mass Spectrom 26:974–985CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Schober Y, Schramm T, Spengler B, Rompp A (2011) Protein identification by accurate mass matrix-assisted laser desorption/ionization imaging of tryptic peptides. Rapid Commun Mass Spectrom 25:2475–2483CrossRefPubMedGoogle Scholar
  65. 65.
    Stauber J, MacAleese L, Franck J, Claude E, Snel M, Kaletas BK, Wiel IM, Wisztorski M, Fournier I, Heeren RM (2010) On-tissue protein identification and imaging by MALDI-ion mobility mass spectrometry. J Am Soc Mass Spectrom 21:338–347CrossRefPubMedGoogle Scholar
  66. 66.
    Gustafsson JO, Eddes JS, Meding S, Koudelka T, Oehler MK, McColl SR, Hoffmann P (2012) Internal calibrants allow high accuracy peptide matching between MALDI imaging MS and LC-MS/MS. J Proteomics 75:5093–5105CrossRefPubMedGoogle Scholar
  67. 67.
    Miladinovic SM, Fornelli L, Lu Y, Piech KM, Girault HH, Tsybin YO (2012) In-spray supercharging of peptides and proteins in electrospray ionization mass spectrometry. Anal Chem 84:4647–4651CrossRefPubMedGoogle Scholar
  68. 68.
    McDonnell LA, Walch A, Stoeckli M, Corthals GL (2014) MSiMass list: a public database of identifications for protein MALDI MS imaging. J Proteome Res 13:1138–1142CrossRefPubMedGoogle Scholar
  69. 69.
    Meding S, Martin K, Gustafsson OJ, Eddes JS, Hack S, Oehler MK, Hoffmann P (2013) Tryptic peptide reference data sets for MALDI imaging mass spectrometry on formalin-fixed ovarian cancer tissues. J Proteome Res 12:308–315CrossRefPubMedGoogle Scholar
  70. 70.
    Thakur D, Rejtar T, Wang D, Bones J, Cha S, Clodfelder-Miller B, Richardson E, Binns S, Dahiya S, Sgroi D, Karger BL (2011) Microproteomic analysis of 10,000 laser captured microdissected breast tumor cells using short-range sodium dodecyl sulfate-polyacrylamide gel electrophoresis and porous layer open tubular liquid chromatography tandem mass spectrometry. J Chromatogr A 1218:8168–8174CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Quanico J, Franck J, Dauly C, Strupat K, Dupuy J, Day R, Salzet M, Fournier I, Wisztorski M (2013) Development of liquid microjunction extraction strategy for improving protein identification from tissue sections. J Proteomics 79:200–218CrossRefPubMedGoogle Scholar
  72. 72.
    Harris GA, Nicklay JJ, Caprioli RM (2013) Localized in situ hydrogel-mediated protein digestion and extraction technique for on-tissue analysis. Anal Chem 85:2717–2723CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Franck J, Quanico J, Wisztorski M, Day R, Salzet M, Fournier I (2013) Quantification-based mass spectrometry imaging of proteins by parafilm assisted microdissection. Anal Chem 85:8127–8134CrossRefPubMedGoogle Scholar
  74. 74.
    Franck J, Arafah K, Elayed M, Bonnel D, Vergara D, Jacquet A, Vinatier D, Wisztorski M, Day R, Fournier I, Salzet M (2009) MALDI imaging mass spectrometry: state of the art technology in clinical proteomics. Mol Cell Proteomics 8:2023–2033CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Fisher R, Pusztai L, Swanton C (2013) Cancer heterogeneity: implications for targeted therapeutics. Br J Cancer 108:479–485CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Turtoi A, Blomme A, Castronovo V (2015) Intratumoral heterogeneity and consequences for targeted therapies. Bull Cancer 102:17–23CrossRefPubMedGoogle Scholar
  77. 77.
    Jones EA, van Remoortere A, van Zeijl RJ, Hogendoorn PC, Bovee JV, Deelder AM, McDonnell LA (2011) Multiple statistical analysis techniques corroborate intratumor heterogeneity in imaging mass spectrometry datasets of myxofibrosarcoma. PLoS One 6:e24913CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Deininger SO, Ebert MP, Futterer A, Gerhard M, Rocken C (2008) MALDI imaging combined with hierarchical clustering as a new tool for the interpretation of complex human cancers. J Proteome Res 7:5230–5236CrossRefPubMedGoogle Scholar
  79. 79.
    Le Faouder J, Laouirem S, Alexandrov T, Ben-Harzallah S, Leger T, Albuquerque M, Bedossa P, Paradis V (2014) Tumoral heterogeneity of hepatic cholangiocarcinomas revealed by MALDI imaging mass spectrometry. Proteomics 14:965–972CrossRefPubMedGoogle Scholar
  80. 80.
    Flatley B, Malone P, Cramer R (2014) MALDI mass spectrometry in prostate cancer biomarker discovery. Biochim Biophys Acta 1844:940–949CrossRefPubMedGoogle Scholar
  81. 81.
    Pagni F, De Sio G, Garancini M, Scardilli M, Chinello C, Smith AJ, Bono F, Leni D, Magni F (2016) Proteomics in thyroid cytopathology: relevance of MALDI-Imaging in distinguishing malignant from benign lesions. Proteomics, published online 31 Mar 2016, doi: 10.1002/pmic.201500448
  82. 82.
    Calligaris D, Feldman DR, Norton I, Olubiyi O, Changelian AN, Machaidze R, Vestal ML, Laws ER, Dunn IF, Santagata S, Agar NY (2015) MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation. Proc Natl Acad Sci U S A 112:9978–9983CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Groseclose MR, Massion PP, Chaurand P, Caprioli RM (2008) High-throughput proteomic analysis of formalin-fixed paraffin-embedded tissue microarrays using MALDI imaging mass spectrometry. Proteomics 8:3715–3724CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Quaas A, Bahar AS, von Loga K, Seddiqi AS, Singer JM, Omidi M, Kraus O, Kwiatkowski M, Trusch M, Minner S, Burandt E, Stahl P, Wilczak W, Wurlitzer M, Simon R, Sauter G, Marx A, Schluter H (2013) MALDI imaging on large-scale tissue microarrays identifies molecular features associated with tumour phenotype in oesophageal cancer. Histopathology 63:455–462PubMedGoogle Scholar
  85. 85.
    Steurer S, Borkowski C, Odinga S, Buchholz M, Koop C, Huland H, Becker M, Witt M, Trede D, Omidi M, Kraus O, Bahar AS, Seddiqi AS, Singer JM, Kwiatkowski M, Trusch M, Simon R, Wurlitzer M, Minner S, Schlomm T, Sauter G, Schluter H (2013) MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays. Int J Cancer 133:920–928CrossRefPubMedGoogle Scholar
  86. 86.
    Steurer S, Seddiqi AS, Singer JM, Bahar AS, Eichelberg C, Rink M, Dahlem R, Huland H, Sauter G, Simon R, Minner S, Burandt E, Stahl PR, Schlomm T, Wurlitzer M, Schluter H (2014) MALDI imaging on tissue microarrays identifies molecular features associated with renal cell cancer phenotype. Anticancer Res 34:2255–2261PubMedGoogle Scholar
  87. 87.
    Steurer S, Singer JM, Rink M, Chun F, Dahlem R, Simon R, Burandt E, Stahl P, Terracciano L, Schlomm T, Wagner W, Hoppner W, Omidi M, Kraus O, Kwiatkowski M, Doh O, Fisch M, Soave A, Sauter G, Wurlitzer M, Schluter H, Minner S (2014) MALDI imaging-based identification of prognostically relevant signals in bladder cancer using large-scale tissue microarrays. Urol Oncol 32:1225–1233CrossRefPubMedGoogle Scholar
  88. 88.
    Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Lokman NA, Zhang C, Anderson L, Scurry J, Leung Y, Stewart CJ, Carter J, Kaur G, Oehler MK, Hoffmann P (2016) Maldi imaging of primary endometrial cancers reveals proteins associated with lymph node metastasis. Proteomics, published online 9 Apr 2016, doi: 10.1002/pmic.201500455
  89. 89.
    Casadonte R, Kriegsmann M, Zweynert F, Friedrich K, Baretton G, Otto M, Deininger SO, Paape R, Belau E, Suckau D, Aust D, Pilarsky C, Kriegsmann J (2014) Imaging mass spectrometry to discriminate breast from pancreatic cancer metastasis in formalin-fixed paraffin-embedded tissues. Proteomics 14:956–964CrossRefPubMedGoogle Scholar
  90. 90.
    Chung L, Phillips L, Lin MZ, Moore K, Marsh DJ, Boyle FM, Baxter RC (2015) A novel truncated form of S100P predicts disease-free survival in patients with lymph node positive breast cancer. Cancer Lett 368:64–70CrossRefPubMedGoogle Scholar
  91. 91.
    Gemoll T, Strohkamp S, Schillo K, Thorns C, Habermann JK (2015) MALDI-imaging reveals thymosin beta-4 as an independent prognostic marker for colorectal cancer. Oncotarget 6:43869–43880CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Harris TM, Du P, Kawachi N, Belbin TJ, Wang Y, Schlecht NF, Ow TJ, Keller CE, Childs GJ, Smith RV, Angeletti RH, Prystowsky MB, Lim J (2015) Proteomic analysis of oral cavity squamous cell carcinoma specimens identifies patient outcome-associated proteins. Arch Pathol Lab Med 139:494–507CrossRefPubMedGoogle Scholar
  93. 93.
    McDonnell LA, Heeren RM, Andren PE, Stoeckli M, Corthals GL (2012) Going forward: Increasing the accessibility of imaging mass spectrometry. J Proteomics 75:5113–5121CrossRefPubMedGoogle Scholar
  94. 94.
    Sarsby J, Martin NJ, Lalor PF, Bunch J, Cooper HJ (2014) Top-down and bottom-up identification of proteins by liquid extraction surface analysis mass spectrometry of healthy and diseased human liver tissue. J Am Soc Mass Spectrom 25:1953–1961CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Wisztorski M, Desmons A, Quanico J, Fatou B, Gimeno JP, Franck J, Salzet M, Fournier I (2016) Spatially-resolved protein surface microsampling from tissue sections using liquid extraction surface analysis. Proteomics, published online 13 Apr 2016, doi: 10.1002/pmic.201500508
  96. 96.
    Wisztorski M, Fatou B, Franck J, Desmons A, Farre I, Leblanc E, Fournier I, Salzet M (2013) Microproteomics by liquid extraction surface analysis: application to FFPE tissue to study the fimbria region of tubo-ovarian cancer. Proteomics Clin Appl 7:234–240CrossRefPubMedGoogle Scholar
  97. 97.
    Quanico J, Franck J, Gimeno JP, Sabbagh R, Salzet M, Day R, Fournier I (2015) Parafilm-assisted microdissection: a sampling method for mass spectrometry-based identification of differentially expressed prostate cancer protein biomarkers. Chem Commun (Camb) 51:4564–4567CrossRefGoogle Scholar
  98. 98.
    Prentice BM, Chumbley CW, Caprioli RM (2015) High-speed MALDI MS/MS imaging mass spectrometry using continuous raster sampling. J Mass Spectrom 50:703–710CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Liu X, Hummon AB (2015) Mass spectrometry imaging of therapeutics from animal models to three-dimensional cell cultures. Anal Chem 87:9508–9519CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Jusal Quanico
    • 1
  • Julien Franck
    • 1
  • Maxence Wisztorski
    • 1
  • Michel Salzet
    • 1
  • Isabelle Fournier
    • 1
  1. 1.Université de Lille 1, INSERM, U1192—Laboratoire ProtéomiqueRéponse Inflammatoire et Spectrométrie de Masse (PRISM)LilleFrance

Personalised recommendations