Reichrath J, Rafi L, Müller S M, Mink D, Reitnauer K, Tilgen W, Schmidt W, Friedrich M
Department of Dermatology, University of the Saarland, Homburg/Saar, Germany.
Histochem J. 1998 Aug;30(8):561-7. doi: 10.1023/a:1003283117492.
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.
在15例正常人宫颈组织和23例宫颈癌组织中，研究了1,25 - 二羟维生素D3受体（VDR）的免疫组化定位及表达。将VDR免疫反应性（单克隆抗体9A7γ）与这些肿瘤中转谷氨酰胺酶K、细胞角蛋白10和Ki - 67的染色模式进行比较。在几乎所有分析的宫颈癌中均检测到VDR呈中度至强核免疫反应性。VDR染色均匀，单个肿瘤细胞之间无视觉差异。约60%的正常宫颈组织显示VDR呈弱免疫反应性。在正常宫颈组织中，核VDR染色局限于宫颈下层，主要在基底细胞层。与正常宫颈组织相比，宫颈癌中VDR免疫染色强度和VDR阳性细胞数量均上调。未发现VDR与增殖和分化标志物的共表达存在视觉相关性。我们的研究结果表明：（1）宫颈组织可能是治疗性应用维生素D类似物的新靶器官；（2）与正常宫颈组织相比，宫颈癌中VDR在蛋白水平上调；（3）宫颈癌中VDR的上调并非仅由上皮分化或增殖的改变引起，而是由不同的未知机制所致；（4）骨化三醇和具有较少高钙血症副作用的新型维生素D类似物可能是治疗或化学预防转移性宫颈癌以及宫颈癌前病变的有前景的新药。
