MALDI Imaging for Proteomic Painting of Heterogeneous Tissue Structures

Abstract

Purpose: To present matrix-assisted laser desorption/ionization (MALDI) imaging as a powerful method to highlight various tissue compartments.

Experimental design: Formalin-fixed paraffin-embedded (FFPE) tissue of a uterine cervix, a pancreas, a duodenum, a teratoma, and a breast cancer tissue microarray (TMA) are analyzed by MALDI imaging and by immunohistochemistry (IHC). Peptide images are visualized and analyzed using FlexImaging and SCiLS Lab software. Different histological compartments are compared by hierarchical cluster analysis.

Results: MALDI imaging highlights tissue compartments comparable to IHC. In cervical tissue, normal epithelium can be discerned from intraepithelial neoplasia. In pancreatic and duodenal tissues, m/z signals from lymph follicles, vessels, duodenal mucosa, normal pancreas, and smooth muscle structures can be visualized. In teratoma, specific m/z signals to discriminate squamous epithelium, sebaceous glands, and soft tissue are detected. Additionally, tumor tissue can be discerned from the surrounding stroma in small tissue cores of TMAs. Proteomic data acquisition of complex tissue compartments in FFPE tissue requires less than 1 h with recent mass spectrometers.

Conclusion and clinical relevance: The simultaneous characterization of morphological and proteomic features in the same tissue section adds proteomic information for histopathological diagnostics, which relies at present on conventional hematoxylin and eosin staining, histochemical, IHC and molecular methods.

Keywords: MALDI imaging; formalin-fixed paraffin-embedded; immunohistochemistry; tumor heterogeneity.