Reis C A, David L, Seixas M, Burchell J, Sobrinho-Simões M
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
Int J Cancer. 1998 Aug 21;79(4):402-10. doi: 10.1002/(sici)1097-0215(19980821)79:4<402::aid-ijc16>3.0.co;2-6.
The membrane-bound MUC1 mucin is expressed in normal mucosas and the aberrant expression of its under-glycosylated forms has been reported in carcinomas from different sites. Several studies have provided conflicting evidence regarding the relationship between MUC1 expression and outcome in cancer patients. In this study, we investigated the immunohistochemical expression of MUC1 epitopes, using 2 monoclonal antibodies (MAbs): HMFG1, which reacts with the fully glycosylated MUC1, was studied in 73 gastric carcinomas; and SM3, which recognises an under-glycosylated form of MUC1, was studied in 180 cases. HMFG1 stained the antrum foveolar cells and the body glands of normal gastric mucosa, whereas SM3 reactivity was restricted to the perinuclear region of some foveolar cells. Type I intestinal metaplasia exhibited down-regulation of MUC1 expression using both MAbs. Every gastric carcinoma was stained with HMFG1 and 80% with SM3. High levels of expression of HMFG1 were associated with lymphatic invasion, nodal metastatization, and advanced pTNM staging. The expression of SM3 was associated with the histologic (solid) type of carcinoma, expanding growth pattern, wall penetration, lymphatic invasion and age of the patients. Despite a trend for a poor outcome in patients with tumours (over)expressing MUC1 mucin, the survival of the patients evaluated by univariate and multivariate analysis was not significantly associated with the levels of expression of HMFG1 or with the expression of the SM3 epitope. We conclude that (a) MUC1 expression, namely of the SM3 cancer-associated epitope, is significantly associated with several aspects of gastric cancer development and progression; and (b) MUC1 expression should not be used as a prognostic marker in patients with gastric carcinoma.
膜结合型MUC1粘蛋白在正常黏膜中表达,其糖基化不足形式的异常表达已在不同部位的癌组织中被报道。关于MUC1表达与癌症患者预后之间的关系,多项研究提供了相互矛盾的证据。在本研究中,我们使用两种单克隆抗体(MAb)研究了MUC1表位的免疫组化表达:HMFG1可与完全糖基化的MUC1反应,在73例胃癌中进行了研究;SM3可识别MUC1的糖基化不足形式,在180例病例中进行了研究。HMFG1可使正常胃黏膜的胃窦小凹细胞和胃体腺染色,而SM3的反应性仅限于一些小凹细胞的核周区域。I型肠化生使用两种单克隆抗体均显示MUC1表达下调。每例胃癌均被HMFG1染色,80%被SM3染色。HMFG1的高表达与淋巴侵犯、淋巴结转移及pTNM分期进展相关。SM3的表达与癌组织的组织学类型(实体型)、浸润性生长方式、壁内浸润、淋巴侵犯及患者年龄相关。尽管MUC1粘蛋白表达(过高)的肿瘤患者有预后不良的趋势,但单因素和多因素分析评估的患者生存率与HMFG1的表达水平或SM3表位的表达无显著相关性。我们得出结论:(a)MUC1表达,即SM3癌相关表位的表达,与胃癌发生和进展的多个方面显著相关;(b)MUC1表达不应作为胃癌患者的预后标志物。