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A study at 911½ñÈÕºÚÁÏ has shown that the way breast cancer samples are routinely preserved in hospitals can alter – or not – the distribution of key metals in the cancer tissue, providing greater clarity on how and when samples can be used in the future to study metal biology.

Researchers in the Department of Earth Science and Engineering (ESE) applied analytical geochemistry techniques – originally developed to study metals in soils and meteorites for example – to explore whether the preservation and preparation of breast cancer tissue for analysis alters the natural distribution of metals like copper, zinc and iron.

Our work marks an important step toward improving how we study biological tissues at the molecular level, and is a great example of how we can adapt methods in our department to answer questions that, at first glance, seem unrelated – all the way to the clinic! Dr Rebekah Moore Research Fellow, Department of Earth Science and Engineering, 911½ñÈÕºÚÁÏ

“These elements play key roles in how cancer grows and spreads, so being able to determine whether the signals we see are coming from the tissues themselves is critical,” said lead author , Research Fellow in Earth Science and Engineering.

“Our work marks an important step toward improving how we study biological tissues at the molecular level, and is a great example of how we can adapt methods in our department to answer questions that, at first glance, seem unrelated – all the way to the clinic!”

A fundamental question for tissue metal imaging

Recent advances in imaging technology have made it possible to create highly detailed maps of metals within biological samples. This technique, known as laser-ablation ICP-MS, provides a new window into the chemistry of cancer.

However, one major question has remained unresolved: whether the processing method used to preserve most surgical tissue samples changes the very metals that researchers are trying to measure.

The study, published , helps answer that question to give scientists greater confidence in using archived patient samples for research. That means we can continue to use samples from existing tissue banks for certain metals, which could lead to discoveries about breast cancer and other cancers, and open doors to new diagnostic or treatment strategies.

“For patients and their families, this work will help to guide researchers planning to study metal distributions in tissues, potentially leading to better understanding of many diseases including cancer,” said first author , PhD student in ESE.

Which metals can be studied reliably?

Most surgical tissue is preserved using a method called FFPE, which allows for long-term storage at room temperature. These archives are a major resource for cancer research but would only be reliable to study metals if the preservation process doesn’t alter the samples’ natural chemistry.

To find out whether this is the case, the team compared fresh-frozen and FFPE breast cancer tissue, focusing on five key metals: magnesium, manganese, iron, copper, and zinc. The tissue samples were analysed by laser-ablation ICP-MS by the at King’s College London.

The good news was that manganese, zinc and iron were largely unaffected, meaning archived samples can be used confidently for studying these elements. However, magnesium levels were affected inconsistently and copper also posed challenges, with blue tissue-marking dyes identified as a likely source of contamination.

“Our findings suggest that if you are studying zinc, manganese or iron, you can probably trust the samples that have been sitting in hospital archives for years. But when it comes to magnesium or copper, sticking to tissue that is freshly frozen after surgery is the safest best to ensure you’re looking at the original chemistry,” said Amy, who previously completed a medical degree at 911½ñÈÕºÚÁÏ before starting a PhD funded by the CRUK Convergence Science Centre.

She added: “These PhD programmes are designed to help train the next generation of clinician-scientists by bringing together science, engineering and clinical medicine. This study reflects that interdisciplinary approach, sitting at the intersection of histopathological practice, analytical chemistry and bioimaging.”

Supporting future breast cancer research

The results are especially important for ongoing work in the Department of Earth Science and Engineering, where researchers – including study authors Dr Moore and – have previously shown that zinc concentrations and isotope compositions differ between normal breast tissue and breast cancer tissue.

Establishing whether zinc distributions are preserved during FFPE processing was therefore an important step in deciding which sample types could be used in future studies. With evidence that zinc remains largely undisturbed, the work supports continued research into how altered distributions of this element reflect the complex biological environment of breast cancer.