Abstract
Microcalcifications are an early mammographic sign of breast cancer and frequent target for stereotactic biopsy. Despite their indisputable value, microcalcifications, particularly of the type II variety that are comprised of calcium hydroxyapatite deposits, remain one of the least understood disease markers. Here we employed Raman spectroscopy to elucidate the relationship between pathogenicity of breast lesions in fresh biopsy cores and composition of type II microcalcifications. Using a chemometric model of chemical-morphological constituents, acquired Raman spectra were translated to characterize chemical makeup of the lesions. We find that increase in carbonate intercalation in the hydroxyapatite lattice can be reliably employed to differentiate benign from malignant lesions, with algorithms based only on carbonate and cytoplasmic protein content exhibiting excellent negative predictive value (93–98%). Our findings highlight the importance of calcium carbonate, an underrated constituent of microcalcifications, as a spectroscopic marker in breast pathology evaluation and pave the way for improved biopsy guidance.
Highlights
In benign duct cysts and only rarely in non-invasive lobular carcinoma in situ[7]
Since the principal goal of the study was to examine the relationship between the chemical composition of hydroxyapatite microcalcifications and the nature of the underlying breast lesion, all further analysis was restricted to these tissue sites harboring such type II microcalcifications
The remaining 73 Raman spectra constituting this data set could be divided according to the histological assessment in the following manner: 42 tissue sites from 15 patients were diagnosed as fibrocystic change (FCC); 17 tissue sites from 6 patients diagnosed as fibroadenoma (FA); and 14 tissue sites from 5 patients diagnosed as invasive ductal carcinoma (IDC; n = 1) or ductal carcinoma in situ (DCIS; n = 13)
Summary
In benign duct cysts and only rarely in non-invasive lobular carcinoma in situ[7]. These oxalate-type microcalcifications are most likely a product of sequestered duct secretions, and are of little clinical concern. There is an urgent, unmet clinical need for a tool that can aid in targeted detection of type II microcalcifications and enable further differentiation between type II microcalcifications associated with benign lesions from those associated with malignancies To address this need, our research has focused on the development of optical spectroscopy, especially Raman scattering, driven primarily by its exquisite molecular specificity and ability to perform real-time measurements in a minimally invasive, non-destructive manner. A more recent FTIR-based investigation by Stone and co-workers supports this conclusion and has shown that the carbonate content of hydroxyapatite microcalcifications decreases with increasing lesion grade[16] All these studies, have been confined to fixed tissue section analyses using microspectroscopy, which represent an important first step but do not address the substantial complexity of real-time fiber probe-based measurements in tissue cores at stereotactic biopsy. The overarching aim of the decision algorithms is to identify spectral markers that can be used to differentiate the nature of the underlying breast lesion associated with type II hydroxyapatite microcalcifications in vivo
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