No abstract

Our findings demonstrate that modulation of VDR expression and local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation of SCCs. Additionally, SCCs represent potential targets for therapy with new vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of calcitriol synthesis/metabolism in these tumors.

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SUMMARYWe investigated immunohistochemically the expression of 1,25 dihydroxy vitamin D 3 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.

No abstract

The immunohistochemical localization and expression of 1,25-dihydroxyvitamin D3 receptors (VDR) has been investigated in normal human cervical tissue (n = 15) and in cervical carcinomas (n = 23). VDR immunoreactivity (monoclonal antibody 9A7gamma) was compared with the staining patterns of transglutaminase K, cytokeratin 10 and Ki-67 in these tumours. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all cervical carcinomas analysed. VDR staining was homogeneous, with no visual differences between individual tumour cells. Some 60% of normal cervical tissues revealed weak immunoreactivity for VDR. In normal cervical tissue, nuclear VDR staining was confined to the lower cervical layers, predominantly to the basal cell layer. Both the intensity of VDR immunostaining and the number of VDR-positive cells were up-regulated in cervical carcinomas compared with normal cervical tissue. No visual correlation was found for the coexpression of VDR with markers of proliferation and differentiation. Our findings indicate that: (1) cervical tissue may be a new target organ for therapeutically applied vitamin D analogues; (2) VDR is up-regulated at the protein level in cervical carcinomas compared with normal cervical tissue; (3) up-regulation of VDR in cervical carcinoma is induced not exclusively by alterations in epithelial differentiation or proliferation, but by different, unknown mechanisms; and (4) calcitriol and new vitamin D analogues exerting fewer calcaemic side-effects may be promising new drugs for the treatment or chemoprevention of metastasizing cervical carcinomas as well as of cervical precancerous lesions.