Chinyama C N, Marshall R E, Owen W J, Mason R C, Kothari D, Wilkinson M L, Sanderson J D
Department of Histopathology, Guy's and St. Thomas' Hospital, London, UK.
Histopathology. 1999 Dec;35(6):517-24. doi: 10.1046/j.1365-2559.1999.00791.x.
Changes in the histochemical characteristics of the surface epithelial mucins is the hallmark of Barrett's metaplasia. The study investigated the pattern of expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma as possible indicators of increased malignant potential.
Tissue sections from 51 patients with Barrett's intestinal metaplasia, nine with dysplasia (three indefinite) and 28 resected adenocarcinomas were stained with monoclonal antibodies to MUC1 and MUC2. The majority of the patients were men (70/88, 80%) who were treated over a period of 3 years. None of the patients with dysplasia or carcinoma were under surveillance at the time of presentation. All 51 biopsies with Barrett's metaplasia expressed MUC2 and MUC1 was consistently absent. Neither MUC1 or MUC2 were expressed in the dysplastic epithelium whether in its pure form (6/6) or when associated with carcinoma (26/28) (P < 0.005). Three biopsies which were initially classified as high-grade dysplasia expressed MUC1 and these turned out to be carcinomas on further investigations. MUC1 was also expressed in 12/28 (43%) of the adenocarcinomas and majority of these were poorly differentiated stage 3 tumours (P < 0.05). MUC2 was only positive in mucin-secreting carcinomas (4/28; 14%) irrespective of the tumour stage.
Despite the large number of patients with Barrett's metaplasia and carcinoma, very few patients presented with dysplasia, implying that Barrett's oesophagus is a silent disease in the community presenting late as carcinoma. The study has demonstrated aberrant expression of MUC2 (an intestinal mucin) in Barrett's metaplasia and this expression is lost when the cells become dysplastic. The lack of MUC1 in dysplastic epithelium and its expression in carcinoma could be utilized as a marker which could differentiate dysplasia from carcinoma in mucosal biopsies. Furthermore, expression of MUC1 in advanced stage oesophageal cancers (as in breast cancer) suggests an unfavourable prognosis.
表面上皮粘蛋白组织化学特性的改变是巴雷特化生的标志。本研究调查了MUC1和MUC2粘蛋白基因产物在巴雷特化生、发育异常和腺癌中的表达模式，作为恶性潜能增加的可能指标。
用抗MUC1和MUC2的单克隆抗体对51例巴雷特肠化生患者、9例发育异常患者（3例不确定）和28例切除的腺癌患者的组织切片进行染色。大多数患者为男性（70/88，80%），治疗时间为3年。在就诊时，发育异常或癌症患者均未接受监测。所有51例巴雷特化生活检均表达MUC2，且始终未表达MUC1。发育异常上皮无论是单纯形式（6/6）还是与癌相关（26/28）时，MUC1和MUC2均未表达（P<0.005）。最初被归类为高级别发育异常的3例活检表达MUC1，进一步检查发现这些均为癌。MUC1也在12/28（43%）的腺癌中表达，其中大多数为低分化3期肿瘤（P<0.05）。MUC2仅在分泌粘蛋白的癌中呈阳性（4/28；14%），与肿瘤分期无关。
尽管有大量巴雷特化生和癌患者，但很少有患者表现出发育异常，这意味着巴雷特食管在社区中是一种隐匿性疾病，晚期表现为癌。该研究已证明MUC2（一种肠粘蛋白）在巴雷特化生中有异常表达，当细胞发育异常时这种表达消失。发育异常上皮中缺乏MUC1及其在癌中的表达可作为一种标志物，用于在黏膜活检中区分发育异常和癌。此外，MUC1在晚期食管癌中的表达（如在乳腺癌中）提示预后不良。
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