Molecular Histology of Tissue using Imaging Mass Spectrometry and Classification Analysis

Abstract

IntroductionImaging mass spectrometry (IMS) applied to fresh frozen or formalin‐fixed tissues enables the visualization of tissue/cancer specific protein/peptide distribution without prior knowledge of the target compounds. Classification analyses of these ion images exhibit strong correlation to high resolution histological images.MethodSerial sections from a tissue microarray (TMA) with formalin‐fixed and paraffin‐embedded (FFPE) normal tissue samples (n=12), cancer samples (n=30) and cell lines (n=16) from different organ sites were analyzed by on‐tissue digestion followed by MALDI imaging and MS/MS analysis.Preliminary dataOn average, 210 high abundance peptides were observed in the mass range from m/z 600–4000. Analyses of serial sections performed on different days and two different instruments showed reproducible patterns. Spectra from various samples, when compared with high resolution histology, showed distinctive differences in peak patterns. For example, peptides detected at m/z 1650.0 and 2089.2 were at significantly higher expression in samples with leiomyosarcoma. Similarly, peptides at m/z 1506.7 and 1177.7 were also seen with significantly higher abundances in pancreas and astrozytoma, respectively.