Mino-Kenudson Mari, Tomita Shigeki, Lauwers Gregory Y
Massachusetts General Hospital Department of Pathology, Boston, MA 02114-2696, USA.
Arch Pathol Lab Med. 2007 Jan;131(1):86-90. doi: 10.5858/2007-131-86-MEIRGA.
Reactive gastropathy is the second most common diagnosis made on gastric biopsies. Increased epithelial proliferation and modifications of epithelial cytokeratin profile, distinct from those of Helicobacter pylori gastritis, have been previously reported. However, the evaluation of mucins, important components of the protective mucosal mucous layer, has not been reported.
To investigate alterations of membrane and secreted mucins in reactive gastropathy of various etiologies using antibodies against mucin glycoproteins.
Thirty-eight gastric biopsies diagnosed as reactive gastropathy, related to nonsteroidal anti-inflammatory drugs (n = 18) or bile reflux (n = 6) or of indeterminate etiology (n = 14), were evaluated using antibodies to MUC1, MUC5AC, MUC6, and MUC2. All cases were confirmed to be negative for H. pylori. The biopsies were classified in 3 groups based on the severity of cytoarchitectural changes (mild, moderate, and severe). Mucin expression and its distribution were recorded and the results correlated with the cytoarchitectural alterations and etiologies.
Loss of MUC1, either patchy or complete, was noted in 67% of the cases. Aberrant expression of MUC5AC in pyloric glands was observed in 81% of the cases, and aberrant expression of MUC6 in the upper foveolar epithelium was diffusely seen in 14% of the cases. Aberrant expression of MUC2 in non-goblet cells was observed in a single case. Aberrant expression of MUC6 was less extensive in the nonsteroidal anti-inflammatory drugs group than in other 2 groups (P = .03). Concurrently, the diffuse distribution of aberrant MUC6 expression was seen only in the cases of severe gastropathy (P = .09). There was no correlation between modifications in expression of other mucins and either the etiologies or the severity of cytoarchitectural changes.
Expressions of membrane (MUC1) and secreted (MUC5AC, MUC6) mucins are frequently modified in reactive gastropathy. The alteration of MUC1, which is involved in cell adhesion and polarity, may play a role in the development of the serrated profile of reactive gastropathy. Milder modifications of the secreted mucins may be explained by the reactive/regenerative nature of the process. Importantly, theses changes are different from the increase in MUC6 and reduction of MUC5AC expression reported in H. pylori gastritis, underlying their mechanistic differences. It is worth noting that similar alterations of mucin expression are shared by various etiologies, that is, nonsteroidal anti-inflammatory drugs and bile reflux, consistent with the nonspecific nature of reactive gastropathy.
反应性胃病是胃活检中第二常见的诊断结果。先前已有报道称,与幽门螺杆菌胃炎不同,反应性胃病存在上皮细胞增殖增加以及上皮细胞角蛋白谱的改变。然而,对于保护性黏膜黏液层的重要组成部分——黏蛋白的评估尚未见报道。
使用针对黏蛋白糖蛋白的抗体,研究各种病因所致反应性胃病中膜性黏蛋白和分泌性黏蛋白的改变。
对38例诊断为反应性胃病的胃活检标本进行评估,这些病例与非甾体抗炎药相关(n = 18)、胆汁反流相关(n = 6)或病因不明(n = 14),使用针对MUC1、MUC5AC、MUC6和MUC2的抗体。所有病例均证实幽门螺杆菌检测为阴性。根据细胞结构变化的严重程度将活检标本分为3组(轻度、中度和重度)。记录黏蛋白的表达及其分布,并将结果与细胞结构改变和病因进行关联分析。
67%的病例出现MUC1的部分或完全缺失。81%的病例在幽门腺中观察到MUC5AC的异常表达,14%的病例在上部小凹上皮中弥漫性观察到MUC6的异常表达。仅在1例非杯状细胞中观察到MUC2的异常表达。非甾体抗炎药组中MUC6的异常表达范围比其他两组小(P = 0.03)。同时,仅在严重胃病病例中观察到异常MUC6表达的弥漫性分布(P = 0.09)。其他黏蛋白表达的改变与病因或细胞结构变化的严重程度之间均无相关性。
在反应性胃病中,膜性黏蛋白(MUC1)和分泌性黏蛋白(MUC5AC、MUC6)的表达经常发生改变。参与细胞黏附和极性的MUC1的改变可能在反应性胃病锯齿状形态的形成中起作用。分泌性黏蛋白的较轻改变可能由该过程的反应性/再生性本质来解释。重要的是,这些变化与幽门螺杆菌胃炎中报道的MUC6增加和MUC5AC表达减少不同,这表明它们在机制上存在差异。值得注意的是,各种病因(即非甾体抗炎药和胆汁反流)均可导致类似的黏蛋白表达改变,这与反应性胃病的非特异性本质一致。