Intermediate to highly suspicious calcification in breast lesions: A radio-pathologic correlation
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong SAR. Breast Cancer Research and Treatment
(Impact Factor: 3.94).
08/2008; 110(1):1-7. DOI: 10.1007/s10549-007-9695-4
Breast calcification is an important feature in the radiological assessment of breast lesions. There are well established diagnostic criteria basing on the morphology and distribution of the calcifications radiologically with recommendation protocols. Pathologically, calcifications in breast lesions are of dystrophic type, and may occur in either the secretory materials or necrotic debris, with inflammation and osteopontin being plausible mediators. Detection of calcium phosphate (hydroyapaptite) is considerably easier than calcium oxalate. Radiologically amorphous calcification represents a borderline type of calcification, and occurs in both benign and malignant (low grade) lesions, and warrants careful follow up and investigation. Clustering of calcification alone may not be an accurate predictor for malignancy, but when there are associated features like pleomorphism, branching, architectural distortion, and associated mass or density, the predictive value for malignant increases. Adequate sampling of calcification in the biopsy is crucial in the management of patients; in general, needle core biopsy or mammotome biopsy achieve satisfactory calcification retrieval. In a benign biopsy that fails to identify the calcifications visible in the mammography, further evaluation or cutting of the histologic block is recommended to minimize the potential of a false negative investigation.
Available from: Stefano Landi
- "Because calcium and vitamin D intake were associated with mechanisms of carcinogenesis of the mammary gland,81,82 and in addition, breast calcifications are an important risk factor for BC,83 Zhang et al84 evaluated the role of miRSNPs within the 3′-UTR of RYR3, a CICR (calcium-induced calcium release) protein playing a crucial role in cellular Ca2+ homeostasis. After the analysis of 1,532 breast cancer cases and 1,600 healthy Chinese women, rs1044129 was found to be associated with BC risk, calcification, and progression-free survival. "
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ABSTRACT: MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression. They have been implicated in a broad range of biological processes, and miRNA-related genetic alterations probably underlie several human diseases. Single nucleotide polymorphisms of transcripts may modulate the posttranscriptional regulation of gene expression by miRNAs and explain interindividual variability in cancer risk and in chemotherapy response. On the basis of recent association studies published in the literature, the present review mainly summarizes the potential role of miRNAs as molecular biomarkers for disease susceptibility, diagnosis, prognosis, and drug-response prediction in tumors. Many clues suggest a role for polymorphisms within the 3' untranslated regions of KRAS rs61764370, SET8 rs16917496, and MDM4 rs4245739 as SNPs in miRNA binding sites highly promising in the biology of human cancer. However, more studies are needed to better characterize the composite spectrum of genetic determinants for future use of markers in risk prediction and clinical management of diseases, heading toward personalized medicine.
Available from: Spyros S Skandalis
- "The standard craniocaudal and lateral views were carried out in all patients. Mammographic findings requiring further exploration with breast biopsy were considered the following: (1) microcalcifications; (2) mass with or without microcalcifications; (3) architectural distortion with or without microcalcifications; and (4) asymmetric density with the greater diameter < 1 cm with or without microcalcifications . Based on published observations, we evaluated MAMCs according to their shape (e.g. "
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ABSTRACT: Mammographic density (MD) and malignant-appearing microcalcifications (MAMCs) represent the earliest mammographic findings of non-palpable breast carcinomas. Matrix proteoglycans versican and decorin are frequently over-expressed in various malignancies and are differently involved in the progression of cancer. In the present study, we have evaluated the expression of versican and decorin in non-palpable breast carcinomas and their association with high risk mammographic findings and tumor characteristics.
Three hundred and ten patients with non-palpable suspicious breast lesions, detected during screening mammography, were studied. Histological examination was carried out and the expression of decorin, versican, estrogen receptor α (ERα), progesterone receptor (PR) and c-erbB2 (HER-2/neu) was assessed by immunohistochemistry.
Histological examination showed 83 out of 310 (26.8%) carcinomas of various subtypes. Immunohistochemistry was carried out in 62/83 carcinomas. Decorin was accumulated in breast tissues with MD and MAMCs independently of the presence of malignancy. In contrast, versican was significantly increased only in carcinomas with MAMCs (median ± SE: 42.0 ± 9.1) and MD (22.5 ± 10.1) as compared to normal breast tissue with MAMCs (14.0 ± 5.8), MD (11.0 ± 4.4) and normal breast tissue without mammographic findings (10.0 ± 2.0). Elevated levels of versican were correlated with higher tumor grade and invasiveness in carcinomas with MD and MAMCs, whereas increased amounts of decorin were associated with in situ carcinomas in MAMCs. Stromal deposition of both proteoglycans was related to higher expression of ERα and PR in tumor cells only in MAMCs.
The specific accumulation of versican in breast tissue with high MD and MAMCs only in the presence of malignant transformation and its association with the aggressiveness of the tumor suggests its possible use as molecular marker in non-palpable breast carcinomas.
Available from: Keith D. Rogers
- "However, it may also be possible that the total mineral content is greater in calcifications of benign lesions. Benign calcifications are typically described as being more crystalline, although this also includes examination of type I (calcium oxalate) calcifications (Tse et al, 2007). The fact that the nature of calcifications (carbonate content and matrix : mineral ratios) in DCIS pathology, appears to lie consistently between benign and invasive types, indicates that benign tissue calcifications (consisting of fibroadenoma, ductal hyperplasia and fibrocystic change) are likely to lead to a DCIS, which in turn will result in invasive disease. "
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ABSTRACT: Breast microcalcifications are key diagnostically significant radiological features for localisation of malignancy. This study explores the hypothesis that breast calcification composition is directly related to the local tissue pathological state.
A total of 236 human breast calcifications from 110 patients were analysed by mid-Fouries transform infrared (FTIR) spectroscopy from three different pathology types (112 invasive carcinoma (IC), 64 in-situ carcinomas and 60 benign). The biochemical composition and the incorporation of carbonate into the hydroxyapatite lattice of the microcalcifications were studied by infrared microspectroscopy. This allowed the spectrally identified composition to be directly correlated with the histopathology grading of the surrounding tissue.
The carbonate content of breast microcalcifications was shown to significantly decrease when progressing from benign to malignant disease. In this study, we report significant correlations (P<0.001) between microcalcification chemical composition (carbonate content and protein matrix : mineral ratios) and distinct pathology grades (benign, in-situ carcinoma and ICs). Furthermore, a significant correlation (P<0.001) was observed between carbonate concentrations and carcinoma in-situ sub-grades. Using the two measures of pathology-specific calcification composition (carbonate content and protein matrix : mineral ratios) as the inputs to a two-metric discriminant model sensitivities of 79, 84 and 90% and specificities of 98, 82 and 96% were achieved for benign, ductal carcinoma in situ and invasive malignancies, respectively.
We present the first demonstration of a direct link between the chemical nature of microcalcifications and the grade of the pathological breast disease. This suggests that microcalcifications have a significant association with cancer progression, and could be used for future objective analytical classification of breast pathology. A simple two-metric model has been demonstrated, more complex spectral analysis may yeild greater discrimination performance. Furthermore there appears to be a sequential progression of calcification composition.
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