BRIEF REPORT |
Correspondence to: Michael Friedrich, Universitäts-Frauenklinik, Gebäude 9, 66421 Homburg/Saar, Germany..
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Summary |
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We investigated immunohistochemically the expression of 1,25 dihydroxy vitamin D3 receptors (VDRs) in normal human breast tissue and in breast carcinomas. For the first time, a VDR immunoreactivity score (VDR-IRS) in breast tissue is presented. Mean VDR-IRS in breast carcinomas was 7.28 compared to 1.55 in normal breast tissue. Comparing staining patterns for VDR and Ki-67, no visual correlation was found, indicating that VDR upregulation in breast carcinomas is not exclusively controlled by the proliferative activity of these tumor cells. Our study adds to the body of evidence that breast tissue may be a sensitive target organ for therapeutically applied new vitamin D analogues that exert few calcemic side effects. (J Histochem Cytochem 46:13351337, 1998)
Key Words: breast carcinoma, VDR score, Ki-67, immunohistochemistry
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Introduction |
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Epidemiological studies have suggested the association of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) deficiency with an increased risk for various malignancies, including colon and breast cancer (
VDRs were detected on frozen sections of breast tissue (lobular carcinomas, n = 7; duct carcinomas, n = 18; normal breast tissue, n = 9) using a previously described and highly sensitive immunohistochemical streptavidinperoxidase technique ( (Dianova; Hamburg, Germany) (
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The steroid hormone responsiveness is directly proportional to the number of corresponding receptors (
It has recently been shown that 1,25(OH)2D3 potentiates TNF-induced cytotoxicity in human cancer cells (
It has been demonstrated that breast carcinomas contain a high percentage of apoptotic cells (
Analyzing coexpression of VDR with markers of proliferation, no visual correlation was found. To assess proliferation of breast tissue, we immunostained specimens using a mouse monoclonal antibody (MAb) directed against Ki-67 antigen (clone Ki-67; Dakopatts, Copenhagen, Denmark) (
Statistical analysis was performed by the Pearson Chi-Square test. No significant correlation was found between VDR-IRS and the histological type of the breast carcinomas analyzed (p=0.731). In addition, VDR-IRS was not statistically significantly correlated with the histological grading of breast carcinomas (p=0.930). No statistically significant correlation was observed between VDR-IRS and Ki-67-IRS (p=0.407). These findings indicate that VDR expression is not exclusively a function of cell proliferation in these tumor cells but is most probably determined additionally by different, currently unknown mechanisms.
To our knowledge, this is the first report presenting a VDR-immunoreactivity score in breast carcinomas. Because VDR mediates the biological effects of 1,25-dihydroxyvitamin D3, VDR upregulation indicates that breast carcinomas may be sensitive target tissues for therapeutically applied new vitamin D analogues that exert few calcemic side effects.
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