Reis C A, David L, Correa P, Carneiro F, de Bolós C, Garcia E, Mandel U, Clausen H, Sobrinho-Simões M
Institute of Molecular Pathology and Immunology of the University of Porto, Portugal.
Cancer Res. 1999 Mar 1;59(5):1003-7.
Intestinal metaplasia is a well-established premalignant condition of the stomach that is characterized by mucin carbohydrate modifications defined by histochemical methods. The purpose of the present study was to see whether the expression of mucin core proteins was modified in the different types of intestinal metaplasia and to evaluate the putative usefulness of mucins as "molecular markers" in this setting. We used a panel of monoclonal antibodies with well-defined specificities to MUC1, MUC2, MUC5AC, and MUC6 to characterize the expression pattern of mucins. In contrast to normal gastric mucosa, the complete form or type I intestinal metaplasia (n = 20) displayed little or no expression of MUC1, MUC5AC, or MUC6 in the metaplastic cells and strong expression of the intestinal mucin MUC2 in the goblet cells of all cases. The incomplete forms of intestinal metaplasia, type II (n = 25) and type III (n = 16), expressed MUC1 and MUC5AC in every case, both in goblet and in columnar cells. MUC6 was also expressed in 16 cases of type II intestinal metaplasia and in 11 cases of type III intestinal metaplasia. The intestinal mucin MUC2 was expressed in every case of incomplete intestinal metaplasia, mostly in goblet cells. The mucin expression profile in the different types of intestinal metaplasia allows the identification of two patterns: one defined by decreased levels of expression of "gastric" mucins (MUC1, MUC5AC, and MUC6) and expression of MUC2 intestinal mucin, which corresponds to type I intestinal metaplasia, and the other defined by coexpression of "gastric mucins" (MUC1, MUC5AC, and MUC6) together with the MUC2 mucin, encompassing types II and III intestinal metaplasia. Our results challenge the classical sequential pathway of intestinal metaplasia (from type I to type III via a type II intermediate step).
肠化生是一种公认的胃癌前病变状态,其特征是通过组织化学方法定义的粘蛋白碳水化合物修饰。本研究的目的是观察不同类型肠化生中粘蛋白核心蛋白的表达是否发生改变,并评估粘蛋白在这种情况下作为“分子标志物”的潜在用途。我们使用了一组对MUC1、MUC2、MUC5AC和MUC6具有明确特异性的单克隆抗体来表征粘蛋白的表达模式。与正常胃黏膜相比,完全型或I型肠化生(n = 20)在化生细胞中几乎不表达或不表达MUC1、MUC5AC或MUC6,而在所有病例的杯状细胞中肠粘蛋白MUC2表达强烈。不完全型肠化生,II型(n = 25)和III型(n = 16),在杯状细胞和柱状细胞中均表达MUC1和MUC5AC。MUC6也在16例II型肠化生和11例III型肠化生中表达。肠粘蛋白MUC2在每例不完全肠化生中均有表达,主要在杯状细胞中。不同类型肠化生中的粘蛋白表达谱可识别出两种模式:一种由“胃”粘蛋白(MUC1、MUC5AC和MUC6)表达水平降低以及MUC2肠粘蛋白表达所定义,这对应于I型肠化生;另一种由“胃粘蛋白”(MUC1、MUC5AC和MUC6)与MUC2粘蛋白共表达所定义,包括II型和III型肠化生。我们的结果对肠化生的经典连续途径(从I型经II型中间步骤到III型)提出了挑战。