High-resolution MALDI-FT-ICR MS imaging for the analysis of metabolites from formalin-fixed, paraffin-embedded clinical tissue samples

J Pathol. 2015 Sep;237(1):123-32. doi: 10.1002/path.4560. Epub 2015 Jun 30.

Abstract

We present the first analytical approach to demonstrate the in situ imaging of metabolites from formalin-fixed, paraffin-embedded (FFPE) human tissue samples. Using high-resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR MSI), we conducted a proof-of-principle experiment comparing metabolite measurements from FFPE and fresh frozen tissue sections, and found an overlap of 72% amongst 1700 m/z species. In particular, we observed conservation of biomedically relevant information at the metabolite level in FFPE tissues. In biomedical applications, we analysed tissues from 350 different cancer patients and were able to discriminate between normal and tumour tissues, and different tumours from the same organ, and found an independent prognostic factor for patient survival. This study demonstrates the ability to measure metabolites in FFPE tissues using MALDI-FT-ICR MSI, which can then be assigned to histology and clinical parameters. Our approach is a major technical, histochemical, and clinicopathological advance that highlights the potential for investigating diseases in archived FFPE tissues.

Keywords: MALDI; cancer; formalin-fixed paraffin-embedded tissue; imaging mass spectrometry; metabolite.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Cluster Analysis
  • Computational Biology
  • Cyclotrons
  • Diagnosis, Differential
  • Disease-Free Survival
  • Female
  • Fixatives / chemistry*
  • Formaldehyde / chemistry*
  • Fourier Analysis
  • Germany
  • Humans
  • Male
  • Metabolomics / methods*
  • Neoplasms / metabolism*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Netherlands
  • Paraffin Embedding*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Time Factors
  • Tissue Fixation / methods*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Fixatives
  • Formaldehyde