Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Videnska 1958, 14021 Prague 4, Czech Republic.
World J Gastroenterol. 2013;19(14):2234-41. doi: 10.3748/wjg.v19.i14.2234.
To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) before and after transplantation.
Eight patients with UC and PSC prior to liver transplantation (PSC-UC), 22 patients with UC after liver transplantation for PSC (OLT), 9 patients with active ulcerative colitis without PSC (UCA), 7 patients with UC in remission (UCR) and 10 controls (N) underwent colonoscopy with multiple biopsies. Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53, Bcl-2 and cyclooxygenase-2 (COX-2) markers. Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests.
PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT, UCA, UCR and N (P < 0.05). We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53 (P < 0.001). UCA had a higher p53 expression as compared to UCR. OLT had a significantly lower expression of p53 as compared with PSC-UC (P < 0.001). Bcl-2 had a significant higher bcl-2 expression as compared with controls. No difference in COX-2 expression between PSC-UC, UCR and UCA was found. UCA had higher COX-2 expression as compared to UCR. We also found a statistically significant positive correlation between the expression of COX-2 and p53. Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSC-UC (P < 0.001). PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score.
Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53, suggesting a higher susceptibility of cancer. This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.
评估长期溃疡性结肠炎（UC）和原发性硬化性胆管炎（PSC）患者在肝移植前后结直肠癌变上皮标志物的表达。
8 例肝移植前患有 UC 和 PSC 的患者（PSC-UC）、22 例因 PSC 行肝移植后的 UC 患者（OLT）、9 例活动性无 PSC 的溃疡性结肠炎患者（UCA）、7 例 UC 缓解期患者（UCR）和 10 例对照者（N）行结肠镜检查并多点活检。对标本进行组织学和半定量免疫组织化学分析，检测 p53、Bcl-2 和环氧化酶-2（COX-2）标志物。采用 Kruskal-Wallis 和 Fisher 确切概率法进行统计学分析。
PSC-UC 非异型增生黏膜中 p53 的表达明显高于 OLT、UCA、UCR 和 N（P < 0.05）。我们还发现 PSC 的发生率与 p53 的表达呈正相关（P < 0.001）。UCA 的 p53 表达高于 UCR。OLT 的 p53 表达明显低于 PSC-UC（P < 0.001）。Bcl-2 的 bcl-2 表达明显高于对照组。PSC-UC、UCR 和 UCA 之间 COX-2 的表达无差异。UCA 的 COX-2 表达高于 UCR。我们还发现 COX-2 的表达与 p53 呈正相关。PSC 行肝移植的患者 p53 的表达明显低于 PSC-UC（P < 0.001）。PSC-UC 的 Mayo 评分与 OLT 和 UCR 相似。
我们的研究表明，PSC 合并 UC 的非异型增生黏膜中抑癌基因 p53 表达较高，提示癌症易感性较高。这种 p53 过表达与 PSC 的存在相关，而在因 PSC 行肝移植的 UC 患者中则不存在。
