LASER ablation inductively coupled plasma mass spectrometry enables the recognition of new patterns in metal-related diseases

In this proof-of-concept study, we devised a calibration method with matrix-matched samples (phantoms) and performed quantitative LASER Ablation Inductively Coupled Mass Spectrometry (LA-ICP-MS) on 16 paraffin embedded human liver samples with genetic hemochromatosis (GH) and 5 liver resection specimens with hepatocellular carcinoma arising on GH, with correlation to histology and integration into our lab's workflow. LA-ICP-MS enables easy recognition of histological structures including portal tracts, fibrous septa and centrilobular veins. Compared to adjacent non-tumoral liver, hepatocellular carcinoma presented a decreased iron concentration (p = 0.034) and no significant difference in copper concentration. This profile was similar to that of three Iron Free Foci identified on genetic hemochromatosis liver biopsies which showed decreased concentration of iron compared to the adjacent parenchyma (p = 0.013) and no significant difference in copper concentration. LA-ICP-MS outperformed Perls' stain for iron detection in liver achieving a detection limit below 1 µg.g-1 and a lateral resolution of 5 μm and can be performed on 3 μm-thick paraffin-embedded slides with few pre-analytics constraints, enabling topographical analysis and quantification, overlay with histological stains and a preservation of the histological material contrary to classic ICP-MS. This new approach opens retrospective analysis of archived histological samples and may prove a tool in the evaluation of metal-related afflictions.