Russell D S, Rassnick K M, Erb H N, Vaughan M M, McDonough S P
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
J Comp Pathol. 2010 Aug-Oct;143(2-3):223-6. doi: 10.1016/j.jcpa.2010.01.019. Epub 2010 Mar 23.
The active form of vitamin D (1alpha, 25-dihydroxycholecalciferol; calcitriol) has potent anti-neoplastic activity in the management of a number of human malignancies. Despite promising data to suggest that calcitriol is an effective adjunct to current chemotherapy modalities, the role of calcitriol in animal neoplasia is poorly understood. Vitamin D inhibits growth of canine mast cell tumours (MCTs) in vitro, presumably due to ligand-mediated activation of the vitamin D receptor (VDR). The aim of the present study was to examine immunohistochemically the expression of the VDR by reactive and neoplastic canine cutaneous mast cells. Expression was graded according to frequency, intensity and score (frequency x intensity). VDR expression was found in all samples containing reactive mast cells (n=9), and in 67 of 69 (97%) MCTs selected from each of the three Patnaik grades. The frequency and score of VDR labelling was greater in MCTs compared with reactive mast cells (P=0.0005 and 0.001, respectively). There was no difference in VDR frequency between the MCT grades, but the frequency of labelling in grade 3 MCTs was higher than for reactive mast cells (P=0.001). There was no association between tumour mitotic index and any of the three VDR variables (all P>0.16). VDR is widely expressed by reactive and neoplastic canine mast cells in vivo. VDR expression is unlikely to represent an independent prognostic factor, but its presence within biopsy specimens might be used to identify patients that are suited to high-dose vitamin D therapeutic trials.
维生素D的活性形式（1α，25 - 二羟胆钙化醇；骨化三醇）在多种人类恶性肿瘤的治疗中具有强大的抗肿瘤活性。尽管有前景的数据表明骨化三醇是当前化疗方式的有效辅助药物，但骨化三醇在动物肿瘤形成中的作用却知之甚少。维生素D在体外可抑制犬肥大细胞瘤（MCT）的生长，推测是由于配体介导的维生素D受体（VDR）激活。本研究的目的是通过免疫组织化学方法检测反应性和肿瘤性犬皮肤肥大细胞中VDR的表达。根据频率、强度和评分（频率×强度）对表达进行分级。在所有含有反应性肥大细胞的样本（n = 9）以及从三种帕特奈克分级中各选取的69个MCT中的67个（97%）中均发现了VDR表达。与反应性肥大细胞相比，MCT中VDR标记的频率和评分更高（分别为P = 0.0005和0.001）。MCT分级之间的VDR频率没有差异，但3级MCT中的标记频率高于反应性肥大细胞（P = 0.001）。肿瘤有丝分裂指数与三个VDR变量中的任何一个均无关联（所有P>0.16）。VDR在体内的反应性和肿瘤性犬肥大细胞中广泛表达。VDR表达不太可能代表一个独立的预后因素，但其在活检标本中的存在可用于识别适合进行高剂量维生素D治疗试验的患者。
