Correlative imaging of benign and cancerous breast calcifications: implications for prognosis and insights into lipid dysregulation
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Kunitake, Jennie A. M. R.
Pathological mineralization is a common phenomenon, though the association between disease state and mineralization ranges from well-established (e.g., heart valve calcification where mineralization defines the disease state) to that of a byproduct, with no known association with disease progression. Breast calcifications, found frequently within benign and cancerous breast tissue, are often classified within the latter category, though their radiological appearances are routinely used for breast cancer screening by mammography, and a body of work has emerged that suggests that their presence may be anything but inert. Despite their unclear causal association with disease, accumulating evidence suggests that breast mineral properties including phase, substitutions, the mineralization extent, and crystallinity are associated with malignancy. The premise of this dissertation is built upon the idea that the calcification process may preserve systemic information about the predisposition of cancer and/or environmental information about the cancer itself that would be recycled or otherwise mobilized in the absence of calcification. One of the driving question of this work is: if information is stored within calcifications, can it be detected and used for breast cancer diagnosis and/or prognosis? The second chapter presented here, explores the mechanisms that surround pathological mineralization, emphasizing cancer and cardiovascular mineralization. Here, with physiological bone remodeling as our touchstone, we propose a context-dependent continuum of cellular involvement with mineralization. The third chapter presents a correlative spectroscopic imaging approach, in series with pathology, to analyze calcifications from benign and cancerous human breast tissue, the foundation of my work. These methods are extended to more patients, with quantitative, clinically relevant results, described in the fourth chapter of this dissertation. One of the most important findings within this chapter suggests an association between calcification organic matrix and disease severity. This association is thematically in keeping with work presented in the fifth chapter where we explore lipid distribution in a 3D model of breast cancer. Consistent with a premise that permeates the cancer community, this chapter suggests that the balance and distribution of lipid species within cancer cells are, at least in part, a function of environment and malignancy. It remains to be seen if the dyshomeostases that so define cancer may be encapsulated within calcifications.
biomineralization; lipidomics; Raman microscopy; whitlockite
Estroff, Lara A.
Donnelly, Eve; Fischbach, Claudia
Materials Science and Engineering
Ph. D., Materials Science and Engineering
Doctor of Philosophy
Attribution 4.0 International
dissertation or thesis
Except where otherwise noted, this item's license is described as Attribution 4.0 International