Fingerprinting Calcium Deposits Provides Cancer Information

An interdisciplinary collaboration in the making used a materials science approach to “fingerprint” the calcium mineral deposits known as microcalcifications that reveal pathological clues to the progression of breast cancer and potentially other diseases. The findings are published in Science Advances. The healthy mineral deposition is a delicately orchestrated process, as seen in bone and tooth formation. Sometimes, however, mineral deposits form in places they don’t belong, such as kidneys – i.e., kidney stones – and breast tissue.

Usually, after the initial mammogram, microcalcifications are largely ignored. And what we’re saying is we can look beyond the resolution of the mammogram, at the microscopic and chemical level, and get more information from these microcalcifications.

Taking well-established, high-resolution characterization techniques from materials science and coupling those with an appreciation for biomineralization and how organisms can control the deposition of minerals resulted in a unique insight into a pathological mineral that may have important implications for disease.

More than a decade ago, researchers started to explore the metastatic spread of breast cancer to bone. This led to an exploration of a “bizarre” phenomenon in which bone-like minerals appeared at primary tumor sites.

From there the collaborators became interested in the ways these microcalcifications can capture elements of the tissue microenvironment where they form, almost like a snapshot. The microenvironment, also known as the organic matrix, can in turn influence the mineral’s composition, morphologies, and mechanical properties.

Minerals forming in breast cancer could be trapping chemical information that reflects their formation environment, and that could potentially have clinical value and relevance. While some cancer biologists have studied microcalcifications, the phenomenon has not been explored by materials scientists.

Microcalcification 'Fingerprints' Can Yield Info About Cancer

Researchers at Memorial Sloan Kettering Cancer Center provided tissue samples containing microcalcifications from 40 breast cancer patients. Next, rather than grind up and homogenize the tissue samples, as other studies had done, the researchers sought to obtain high-resolution, three-dimensional maps of the chemistry of the mineral and the organic matrix.

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So they used a vibrational spectroscopy technique called Raman microscopy that can detect the distinct vibrational signatures of a biological molecule’s organic and inorganic chemistries, and also map where those signatures are occurring.

Using hierarchical clustering, they could look at our data as a heatmap, and that gave us an idea of how different parameters that we measured were related to one another, and how the different calcifications grouped based on their fingerprints.

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Cancer-associated microcalcifications cluster into physiologically relevant groups that reflect the tissue type and local malignancy; mineral carbonate exhibits substantial variety inside the tumor; trace metals – including zinc, iron, and aluminum – are enhanced in malignant-localized calcifications; and the ratio of lipids to proteins within microcalcifications is lower in patients with poor prognosis.

While the researchers are not sure if the microcalcifications form before cancer develops or because of it, the findings indicate there is a correlation with disease severity. The researchers are hopeful the findings may also illuminate calcifications in other types of cancer, such as thyroid and ovarian cancer.

The team now plans to study a larger spread of disease characteristics, and also apply their approach to other pathological mineralization diseases, such as calcific aortic valve disease, in which mineral forms in the heart valve.



Source-Eurekalert