There is currently extensive diagnostic use of breast tissue calcifications through their differential mammographic appearance, albeit with relatively low specificity. However, the details of the calcification chemical and structural composition remain somewhat vague. Thus any associated clinical significance, such as indications of tumour type, grade and stage, have not previously been explored.
Methods
The biochemical composition and incorporation of carbonate into the hydroxyapatite lattice of type II microcalcifications was studied by infrared microspectroscopy, allowing spectral information to be directly correlated with associated histopathology of the surrounding tissue.
Results
It was shown that the chemical characteristics of calcifications associated with benign, in situ and invasive pathologies are significantly different. For the first time, a relationship between grade of pathological breast disease and chemical nature of associated microcalcifications has been demonstrated. In particular we have found significant correlations between distinct pathology grades and physiochemical features such as the carbonate content of microcalcifications and protein to mineral ratios. Further, such correlations were also demonstrated within carcinoma in situ and invasive cancer subgrades. Quantification of the calcification carbonate content indicated that the degree of carbonate substitution followed a monotonic trend between benign, ductal carcinoma in situ (DCIS) and invasive pathologies (see Figure 1). This suggests that benign tissue calcification (consisting of fibroadenoma, ductal hyperplasia and fibrocystic change) is likely to lead to a DCIS, which in turn will result in invasive disease.
Figure 1
Apatite %CO32-for each pathology group.
Conclusions
This study a greater significance for microcalcification chemistry in mechanisms associated with cancer progression, and especially for the future diagnosis and classification of breast pathology.
