title: Classification of HER2 receptor status in breast cancer tissues by MALDI imaging mass spectrometry.
abstract: Clinical laboratory testing for HER2 status in breast cancer tissues is critically important for therapeutic decision making. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating proteins through the direct and morphology-driven analysis of tissue sections. We hypothesized that MALDI-IMS may determine HER2 status directly from breast cancer tissues. Breast cancer tissues (n = 48) predefined for HER2 status were subjected to MALDI-IMS, and protein profiles were obtained through direct analysis of tissue sections. Protein identification was performed by tissue microextraction and fractionation followed by top-down tandem mass spectrometry. A discovery and an independent validation set were used to predict HER2 status by applying proteomic classification algorithms. We found that specific protein/peptide expression changes strongly correlated with the HER2 overexpression. Among these, we identified m/z 8404 as cysteine-rich intestinal protein 1. The proteomic signature was able to accurately define HER2-positive from HER2-negative tissues, achieving high values for sensitivity of 83%, for specificity of 92%, and an overall accuracy of 89%. Our results underscore the potential of MALDI-IMS proteomic algorithms for morphology-driven tissue diagnostics such as HER2 testing and show that MALDI-IMS can reveal biologically significant molecular details from tissues which are not limited to traditional high-abundance proteins.
authors.affiliation: Institute of Pathology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, Neuherberg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rauser
authors.forename: Claudio
authors.initials: C
authors.lastname: Marquardt
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balluff
authors.forename: Sören-Oliver
authors.initials: SO
authors.lastname: Deininger
authors.forename: Christian
authors.initials: C
authors.lastname: Albers
authors.forename: Eckhard
authors.initials: E
authors.lastname: Belau
authors.forename: Ralf
authors.initials: R
authors.lastname: Hartmer
authors.forename: Detlev
authors.initials: D
authors.lastname: Suckau
authors.forename: Katja
authors.initials: K
authors.lastname: Specht
authors.forename: Matthias Philip
authors.initials: MP
authors.lastname: Ebert
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmitt
authors.forename: Michaela
authors.initials: M
authors.lastname: Aubele
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry / Q000201:enzymology*; D002352:Carrier Proteins; D016000:Cluster Analysis; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D060588:LIM Domain Proteins; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D060588:LIM Domain Proteins; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C486181:CRIP1 protein, human; C508053:ERBB2 protein, human