Classification of HER2 receptor status in breast cancer tissues by MALDI imaging mass spectrometry.
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.
Rauser
Sandra
S
Institute of Pathology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, Neuherberg, Germany.
Marquardt
Claudio
C
Balluff
Benjamin
B
Deininger
Sören-Oliver
SO
Albers
Christian
C
Belau
Eckhard
E
Hartmer
Ralf
R
Suckau
Detlev
D
Specht
Katja
K
Ebert
Matthias Philip
MP
Schmitt
Manfred
M
Aubele
Michaela
M
Höfler
Heinz
H
Walch
Axel
A
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*
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