Bryan R T, Nicholls J H, Harrison R F, Jankowski J A, Wallace D M A
Epithelial Laboratory, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK.
J Urol. 2003 Nov;170(5):1892-6. doi: 10.1097/01.ju.0000092740.51330.39.
Chronic inflammation is a risk factor for malignant transformation in the bladder. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) is a mediator of such inflammation that induces nuclear localization of the adherens junction component beta-catenin. This mechanism has a key role in the initiation and progression of the premalignant lesion Barrett's metaplasia of the esophagus. Cystitis glandularis is a metaplastic lesion of the bladder urothelium occurring in the presence of chronic inflammation and in up to 13% of asymptomatic bladders. Two subtypes are described (typical and intestinal/colonic) with uncertain malignant potential. Etiologically and histologically cystitis glandularis mimics Barrett's metaplasia. We investigated the roles of beta-catenin and TNFalpha in cystitis glandularis.
Immunohistochemistry and immunofluorescence were used to demonstrate the expression and localization of E-cadherin, beta-catenin and TNFalpha in 9 sections of typical cystitis glandularis and 4 of intestinal/colonic cystitis glandularis. Appropriate controls were used for all experiments.
Immunohistochemistry demonstrated normal membranous expression of E-cadherin and beta-catenin in all cystitis glandularis sections with increased TNFalpha expression. Immunofluorescence showed nuclear localization of beta-catenin in the intestinal/colonic subtype only, which was not observed in typical cystitis glandularis.
The presence of nuclear beta-catenin suggests that intestinal/colonic cystitis glandularis shares the same signaling pathway with the premalignant lesion Barrett's metaplasia of the esophagus and the intestinal/colonic subtype of cystitis glandularis may have the potential to progress to malignancy. This finding has important implications for the management of this lesion.
慢性炎症是膀胱恶性转化的一个危险因素。促炎细胞因子肿瘤坏死因子-α（TNFα）是这种炎症的介质，可诱导黏附连接成分β-连环蛋白的核定位。该机制在食管癌前病变巴雷特化生的发生和发展中起关键作用。腺性膀胱炎是膀胱尿路上皮的一种化生病变，发生于慢性炎症存在时，在高达13%的无症状膀胱中也可出现。描述了两种亚型（典型型和肠型/结肠型），其恶性潜能不确定。在病因和组织学上，腺性膀胱炎类似于巴雷特化生。我们研究了β-连环蛋白和TNFα在腺性膀胱炎中的作用。
采用免疫组织化学和免疫荧光法检测9例典型腺性膀胱炎和4例肠型/结肠型腺性膀胱炎切片中E-钙黏蛋白、β-连环蛋白和TNFα的表达及定位。所有实验均使用了适当的对照。
免疫组织化学显示，所有腺性膀胱炎切片中E-钙黏蛋白和β-连环蛋白呈正常膜表达，TNFα表达增加。免疫荧光显示，仅在肠型/结肠型亚型中观察到β-连环蛋白的核定位，在典型腺性膀胱炎中未观察到。
β-连环蛋白核内存在提示肠型/结肠型腺性膀胱炎与食管癌前病变巴雷特化生具有相同的信号通路，肠型/结肠型腺性膀胱炎亚型可能具有进展为恶性肿瘤的潜能。这一发现对该病变的处理具有重要意义。
