Immunohistochemical analysis of 1,25-dihydroxyvitamin-D3-receptors, estrogen and progesterone receptors and Ki-67 in ovarian carcinoma.

ABSTRACT

BACKGROUND: The aim of this study was to analyze immunohistochemically the expression of VDR in normal and carcinomatous ovarian tissue to evaluate whether ovarian tissue may be a new potential target for biologically active vitamin D analogues. MATERIALS AND METHODS: The expression of 1,25-dihydroxyvitamin-D3-receptors (VDR) was immunohistochemically investigated in ovarian carcinomas (n=40). VDR immunoreactivity (mAb 9A7gamma) was compared with the staining pattern of the proliferation marker Ki-67, of the estrogen receptors (ER) and of the progesterone receptors (PR). The percentage of positive tumour cells (PP), the intensity of staining (SI) and a resulting immunoreactivity score (IRS) were determined for the semiquantitative evaluation of VDR-, ER- and PR-expression. RESULTS: A total of 16.7% of the normal surface ovarian epithelium was VDR-negative, while the remaining 83.3% revealed weak to moderate VDR immunoreactivity. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all ovarian carcinomas analyzed. Both the intensity of VDR immunostaining and the number of VDR-positive cells were significantly increased in ovarian carcinomas as compared to normal ovarian tissue. Analyzing coexpression of VDR with the proliferation marker Ki-67 or with the estrogen and progesterone receptors, no significant correlation was found. CONCLUSION: Our findings indicate that (I) VDR expression is increased in ovarian carcinomas as compared to normal ovarian tissue. (II) Up-regulation of VDR in ovarian carcinomas is not exclusively induced by an increase of proliferation, but by different unknown mechanisms. (III) Expression of VDR in ovarian carcinomas is independently regulated from the expression of ER and PR. (IV) Ovarian tissue may be a new target organ for therapeutically applied vitamin D analogues exerting fewer calcemic side-effects. New vitamin D analogues may be promising drugs for the treatment of advanced ovarian carcinomas.