IMMUNOHISTOCHEMICAL ANALYSIS OF 1,25-DIHYDROXYVITAMIN D-3 RECEPTOR INCERVICAL-CARCINOMA

The immunohistochemical localization and expression of 1,25-dihydroxyv itamin D-3 receptors (VDR) has been investigated in normal human cervi cal tissue (n = 15) and in cervical carcinomas (n = 23). VDR immunorea ctivity (monoclonal antibody 9A7 gamma) was compared with the staining patterns of transglutaminase K, cytokeratin 10 and Ki-67 in these tum ours. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all cervical carcinomas analysed. VDR staining was homogene ous, 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 l ower cervical layers, predominantly to the basal cell layer. Both the intensity of VDR immunostaining and the number of VDR-positive cells w ere up-regulated in cervical carcinomas compared with normal cervical tissue. No visual correlation was found for the coexpression of VDR wi th markers of proliferation and differentiation. Our findings indicate that: (1) cervical tissue may be a new target organ for therapeutical ly 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 exclusivel y by alterations in epithelial differentiation or proliferation, but b y different, unknown mechanisms; and (4) calcitriol and n MT vitamin D analogues exerting fewer calcaemic side-effects may be promising new drugs for the treatment or chemoprevention of metastasizing cervical c arcinomas as well as of cervical precancerous lesions. (C) 1998 Chapma n & Hall.