Matrix-assisted laser desorption/ionization mass spectrometry imaging for spatial clinical oncopathology: diagnosis,...

Area of Science:

• Oncology
• Analytical Chemistry
• Pathology

Background:

• Clinical oncology relies on molecular data, but current assays often disconnect analytes from diagnostic histological context.
• Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) emerges as a spatial molecular tool for direct tissue analysis.

Purpose of the Study:

• To review the applications of MALDI-MSI in refining conventional oncopathology.
• To assess the potential of spatial molecular evidence in diagnostics, margin assessment, tumor microenvironment interpretation, and treatment response prediction.

Main Methods:

• Evaluation of existing literature on MALDI-MSI applications in oncology.
• Focus on integrating spatial molecular data with hematoxylin and eosin (H&E) morphology and expert annotation.
• Exploration of advancements from visual comparison to multimodal registration and machine learning.

Main Results:

• MALDI-MSI shows progress in molecularly resolved histology, margin assessment, tumor microenvironment analysis, and predicting therapeutic response.
• Advancements include multimodal registration, machine learning, spatial proteomics, and spatial pharmacology.
• Clinical value hinges on alignment with H&E morphology, annotation, quality control, and validation.

Conclusions:

• Routine adoption of MALDI-MSI is limited by pre-analytical variability, annotation gaps, batch effects, and validation issues.
• The most feasible near-term role for MALDI-MSI is as a spatial molecular adjudicator for specific clinical challenges.
• MALDI-MSI can aid in difficult classifications, uncertain margins, field effects, microenvironment risk, and drug exposure assessment.