Wada Koji, Tanaka Hiroaki, Maeda Kiyoshi, Inoue Toru, Noda Eiji, Amano Ryosuke, Kubo Naoshi, Muguruma Kazuya, Yamada Nobuya, Yashiro Masakazu, Sawada Tetsuji, Nakata Bunzo, Ohira Masaichi, Hirakawa Kosei
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Oncol Rep. 2009 Nov;22(5):1021-5. doi: 10.3892/or_00000530.
Since the 1970s, it has been well known that long-standing ulcerative colitis (UC) disposes to the development of colorectal adenocarcinoma (CRC). To date, CRC associated with UC is thought to arise along a pathway of dysplasia, however, primary factors for developing of UC-related dysplasia and cancer are unclear. Vitamin D, which works through binding the vitamin D receptor (VDR) has an important role in cancer progression and immune response. In this study, we investigated the impact of VDR expression on UC as well as colon cancer. We examined retrospectively the expression of VDR in extraction specimens of UC (n=124) patients by immunohistochemistry. We counted VDR positive cells in at least 10 fields in each case to evaluate the frequency of VDR positive cells in ductal epithelium. In addition, effect of VDR expression on inflammation was analyzed. On a normal mucosa, the expression of VDR was recognized in 58.8% of ductal cells. In UC patient, the expression of VDR was considerably decreased compared to normal mucosa, VDR positive rate was only 3.4+/-9.0%. Importantly, dysplasia and UC-CRC patients showed lower rate of VDR expression compared to non-colon cancer patients, whose expression rates were 0.6+/-1.3% and 3.8+/-10%, respectively. Moreover, long-term UC patients (more than ten years) who were at high-risk of developing CRC showed significantly lower VDR expression than short-term patients. We did not detect direct association of VDR expression with inflammation and clinical stage of UC. These findings suggested that correlation seems to exist between the level of VDR expression and carcinogenesis in UC. VDR could be a possible marker to detect dysplasia and cancer in ulcerative colitis.
自20世纪70年代以来，人们就已经清楚地知道，长期存在的溃疡性结肠炎（UC）易患结直肠癌（CRC）。迄今为止，与UC相关的CRC被认为是沿着发育异常的途径发生的，然而，UC相关发育异常和癌症发生的主要因素尚不清楚。通过与维生素D受体（VDR）结合发挥作用的维生素D在癌症进展和免疫反应中具有重要作用。在本研究中，我们调查了VDR表达对UC以及结肠癌的影响。我们通过免疫组织化学回顾性检查了UC患者（n = 124）提取标本中VDR的表达。我们在每个病例的至少10个视野中计数VDR阳性细胞，以评估导管上皮中VDR阳性细胞的频率。此外，分析了VDR表达对炎症的影响。在正常黏膜上，58.8%的导管细胞中可识别出VDR的表达。在UC患者中，与正常黏膜相比，VDR的表达明显降低，VDR阳性率仅为3.4±9.0%。重要的是，发育异常和UC-CRC患者的VDR表达率低于非结肠癌患者，其表达率分别为0.6±1.3%和3.8±10%。此外，处于CRC高风险的长期UC患者（超过十年）的VDR表达明显低于短期患者。我们未检测到VDR表达与UC的炎症和临床分期之间存在直接关联。这些发现表明，VDR表达水平与UC中的致癌作用之间似乎存在相关性。VDR可能是检测溃疡性结肠炎中发育异常和癌症的一个可能标志物。
