Zinc stable isotope analysis reveals Zn dyshomeostasis in benign tumours, breast cancer, and adjacent histologically normal tissue

The disruption of Zn homeostasis has been linked with breast cancer development and progression. To enhance our understanding of changes in Zn homeostasis both inside and around the tumour microenvironment, Zn concentrations and isotopic compositions (delta Zn-66) were determined in benign (BT) and malignant (MT) tumours, healthy tissue from reduction mammoplasty (HT), and histologically normal tissue adjacent to benign (NAT(BT)) and malignant tumours (NAT(MT)). Mean Zn concentrations in NAT(BT) are 5.5 mu g g(-1) greater than in NAT(MT) (p = 0.00056) and 5.1 mu g g(-1) greater than in HT (p = 0.0026). Zinc concentrations in MT are 12.9 mu g g(-1) greater than in HT (p = 0.00012) and 13.3 mu g g(-1) greater than in NAT(MT) (p < 0.0001), whereas delta Zn-66 is 0.17 parts per thousand lower in MT than HT (p = 0.017). Benign tumour Zn concentrations are also elevated compared to HT (p = 0.00013), but are not significantly elevated compared to NAT(BT) (p = 0.32). The delta Zn-66 of BT is 0.15 parts per thousand lower than in NAT(BT) (p = 0.045). The similar light delta Zn-66 of BT and MT compared to HT and NAT may be related to the isotopic compensation of increased metallothionein (Zn-64-rich) expression by activated matrix metalloproteinase (Zn-66-rich) in MT, and indicates a resultant Zn-66-rich reservoir may exist in patients with breast tumours. Zinc isotopic compositions thus show promise as a potential diagnostic tool for the detection of breast tumours. The revealed differences of Zn accumulation in healthy and tumour-adjacent tissues require additional investigation.

Automated summary

The disruption of Zn homeostasis is associated with breast cancer development and progression. Zinc concentrations and isotopic compositions were analyzed in different types of tissues, showing significant differences between benign and malignant tumours as well as healthy tissues. Zinc isotopic compositions have potential as a diagnostic tool for breast tumours, while further investigation into Zn accumulation in tissues is needed.