Imaging of Esophageal Lymph Node Metastases by Desorption Electrospray Ionization Mass Spectrometry

Abstract

Histopathological assessment of lymph node metastases (LNM) depends on subjective analysis of cellular morphology with inter-/intra-observer variability. In this study, LNM from esophageal adenocarcinoma was objectively detected using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Ninety lymph nodes and their primary tumor biopsies from 11 esophago-gastrectomy specimens were examined and analyzed by DESI-MSI. Images from mass spectrometry and corresponding histology were co-registered and analyzed using multivariate statistical tools. The MSIs revealed consistent lipidomic profiles of individual tissue types found within lymph nodes. Spatial mapping of the profiles showed identical distribution patterns as per the tissue types in matched immunohistochemistry images. Lipidomic profile comparisons of LNM versus the primary tumor revealed a close association in contrast to benign lymph node tissue types. This similarity was used for the objective prediction of LNM in mass spectrometry images utilizing the average lipidomic profile of esophageal adenocarcinoma. The multivariate statistical algorithm developed for LNM identification demonstrated a sensitivity, specificity, positive predictive value and negative predictive value of 89.5, 100, 100 and 97.2 per-cent, respectively, when compared to gold-standard immunohistochemistry. DESI-MSI has the potential to be a diagnostic tool for peri-operative identification of LNM and compares favorably with techniques currently used by histopathology experts.

Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces

“…The primary goal of DESI applications has been to focus on the small molecules released, for example in the real‐time detection of tumour tissue during surgical procedures 3, 4. While DESI has also been adapted to study large biomolecules, via the mixing of ES droplets and solution in a process known as liquid DESI,5, 6 it has not yet been applied to proteins deposited on surfaces and desorbed in solutions that retain their native state interactions.…”

Ambient mass spectrometry in metabolomics

“…80 Identification of lymph node micro- and macrometastases was achieved with a sensitivity of 89.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 97.2% when compared with standard IHC. 80 …”

“…Applications include fast diagnostics, 66–72 biomarker discovery, 68, 73 intraoperative tissue characterization, 74–79 molecular imaging, 14, 80–96 and drug metabolism. 97–102 Specific to cancer research are the capabilities offered by ambient MS techniques comprising the determination of boundaries between cancerous and non-cancerous tissues based on ion fingerprints, the discovery of potential biomarkers for diagnosis and prognosis, and the monitoring of drug metabolites to evaluate chemotherapy efficacy, as illustrated by some of the examples that follow.…”

“…87 Additional examples illustrating the contributions and further potential of DESI-MSI in cancer research exist in the literature. 80, 81, 90, 93 A DESI-MSI-based method based on PCA of lipidomic profiles, for example, allowed identifying specific lymph node tissue types without the need for immunohistochemistry (IHC) experiments. 80 Identification of lymph node micro- and macrometastases was achieved with a sensitivity of 89.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 97.2% when compared with standard IHC.…”

Lipidomics for translational skin research: A primer for the uninitiated

“…Unlike MALDI‐MSI, no matrix is required, so skin tissue simply requires sectioning prior to analysis. DESI‐MSI has proven capabilities in imaging of lipids across tissues, but until recently has lacked the spatial resolution to analyse intricate tissues such as skin, with typical pixel sizes around 100 μm …”