Journal
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
Volume 303, Issue 1, Pages 195-205Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00404-020-05789-8
Keywords
Breast cancer; Zinc; Laser ablation inductively coupled mass spectrometry (LA-ICPMS); Steroid receptor; Human epidermal growth factor receptor 2; Biomarker
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Funding
- Projekt DEAL
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This study demonstrated the feasibility of LA-ICPMS for analyzing zinc content in breast cancer tissue, showing a correlation between zinc accumulation and histological grading and molecular subtypes. Zinc levels were found to be highest in high-risk cancers, particularly in Her2-positive and triple-negative disease.
Purpose To show feasibility of laser ablation inductively coupled mass spectrometry (LA-ICPMS) for analysis of zinc content and concentration in breast cancer tissue and to correlate this with validated prognostic and predictive markers, i.e. histological grading and expression of steroid receptors (estrogen receptor, ER; progesterone receptor, PR) and human epidermal growth-factor receptor 2 (Her2). Methods 28 samples of human invasive ductal breast cancer tissue were subclassified into groups of four different intrinsic subtypes according to the expression of ER, PR and Her2 by immunohistological staining and then analyzed for zinc content and distribution by LA-ICPMS applying a calibration technique based on spiked polyacrylamide gels. A correlation of zinc concentration with histological grading and molecular subtypes was analyzed. Results Consistent with results of a pilot-study LA-ICPMS was feasible to show zinc accumulation in cancerous tissue, even more adjacent healthy stroma was with proportional increase of zinc. Zinc levels were most elevated in triple-positive (TPBC) and in triple-negative (TNB) breast cancers. Conclusion LA-ICPMS was feasible to confirm a connection between zinc and grade of malignancy; furthermore, focusing on a correlation of zinc and intrinsic breast cancer subtypes, LA-ICPMS depicted an upwards trend of zinc for high-risk-cancers with highest levels in Her2-positive and in triple-negative (TNBC) disease. The currently uncommon alliance of clinicians and analytical chemists in basic research is most promising to exploit the full potential of diagnostic accuracy in the efforts to solve the enigma of breast cancer initiation and course of disease.
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