title: Molecular profiles of thyroid cancer subtypes: Classification based on features of tissue revealed by mass spectrometry imaging.
abstract: Determination of the specific type of thyroid cancer is crucial for the prognosis and selection of treatment of this malignancy. However, in some cases appropriate classification is not possible based on histopathological features only, and it might be supported by molecular biomarkers. Here we aimed to characterize molecular profiles of different thyroid malignancies using mass spectrometry imaging (MSI) which enables the direct annotation of molecular features with morphological pictures of an analyzed tissue. Fifteen formalin-fixed paraffin-embedded tissue specimens corresponding to five major types of thyroid cancer were analyzed by MALDI-MSI after in-situ trypsin digestion, and the possibility of classification based on the results of unsupervised segmentation of MALDI images was tested. Novel method of semi-supervised detection of the cancer region of interest (ROI) was implemented. We found strong separation of medullary cancer from malignancies derived from thyroid epithelium, and separation of anaplastic cancer from differentiated cancers. Reliable classification of medullary and anaplastic cancers using an approach based on automated detection of cancer ROI was validated with independent samples. Moreover, extraction of spectra from tumor areas allowed the detection of molecular components that differentiated follicular cancer and two variants of papillary cancer (classical and follicular). We concluded that MALDI-MSI approach is a promising strategy in the search for biomarkers supporting classification of thyroid malignant tumors. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, ul. Wybrzeze Armii Krajowej 15, 44101 Gliwice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Pietrowska
authors.affiliation: Medizinisches Proteom-Center, Ruhr-University Bochum, Universitätsstraße 150, 44801 Bochum, Germany.
authors.forename: Hanna C
authors.initials: HC
authors.lastname: Diehl
authors.affiliation: Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, ul. Akademicka 16, 44100 Gliwice, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Mrukwa
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, ul. Wybrzeze Armii Krajowej 15, 44101 Gliwice, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kalinowska-Herok
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, ul. Wybrzeze Armii Krajowej 15, 44101 Gliwice, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Gawin
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, ul. Wybrzeze Armii Krajowej 15, 44101 Gliwice, Poland.
authors.forename: Mykola
authors.initials: M
authors.lastname: Chekan
authors.affiliation: Medizinisches Proteom-Center, Ruhr-University Bochum, Universitätsstraße 150, 44801 Bochum, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Elm
authors.affiliation: Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, ul. Akademicka 16, 44100 Gliwice, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Drazek
authors.affiliation: Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, ul. Akademicka 16, 44100 Gliwice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Krawczyk
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, ul. Wybrzeze Armii Krajowej 15, 44101 Gliwice, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Lange
authors.affiliation: Medizinisches Proteom-Center, Ruhr-University Bochum, Universitätsstraße 150, 44801 Bochum, Germany; Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Bunsen-Kirchhoff-Straße 11, 44139 Dortmund, Germany.
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.affiliation: Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, ul. Akademicka 16, 44100 Gliwice, Poland. Electronic address: joanna.polanska@polsl.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Polanska
authors.affiliation: Medizinisches Proteom-Center, Ruhr-University Bochum, Universitätsstraße 150, 44801 Bochum, Germany; Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Bunsen-Kirchhoff-Straße 11, 44139 Dortmund, Germany. Electronic address: corinna.henkel@isas.de.
authors.forename: Corinna
authors.initials: C
authors.lastname: Henkel
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, ul. Wybrzeze Armii Krajowej 15, 44101 Gliwice, Poland. Electronic address: piotr.widlak@io.gliwice.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Widlak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D002648:Child; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D000072637:Thyroid Epithelial Cells / Q000378:metabolism / Q000473:pathology; D013961:Thyroid Gland / Q000378:metabolism / Q000502:physiology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Classification; FFPE tissue; Mass spectrometry imaging; Molecular signature; Thyroid cancer