Immunoreactivity of Lewis blood group and mucin peptide core antigens:: Correlations with grade of dysplasia and malignant transformation in the colorectal adenoma-carcinoma sequence

Immunoreactivity of Lewis blood group and mucin peptide core antigens:: Correlations with grade of dysplasia and malignant transformation in the colorectal adenoma-carcinoma sequence
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DOI:
10.14670/hh-17.191
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发表时间:
2002-01-01
影响因子:
2
通讯作者:
Dienes, HP
Dienes, HP
中科院分区:
生物学4区
文献类型:
--
作者:
Baldus, SE;Hanisch, FG;Dienes, HP

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以往关于各种粘蛋白肽和碳水化合物抗原在结直肠肿瘤组织中的免疫反应性的研究结果至少在一定程度上是相互矛盾的。因此,我们采用免疫组化方法,应用针对Lewis血型抗原(唾液酰-Le(a)、Le(x)、唾液酰-Le(x)、Le(y))和黏液蛋白肽核(MUC1、MUC2和MUC5AC)的单克隆抗体(maabs)对42例腺瘤和44例癌进行了研究。结直肠腺瘤中高度发育不良的发生与Ley和MUC1表位的免疫反应性呈统计学显著正相关,而MUC2表位呈显著负相关。其他表位的反应性与恶性转化的进展没有关联。结直肠癌根据其组织病理学亚型进行细分。免疫组化染色结果显示黏液腺癌与管状腺癌的MUC2反应性明显增强。muc1特异性单抗不与完全糖基化的肽核发生反应,其免疫反应性显示出统计学上不显著的反向趋势,而所有碳水化合物抗原在两种肿瘤亚型中均表现出强表达。此外,粘蛋白肽和碳水化合物表位标记之间的相关性进行了评估。与MUC2免疫反应性相比,腺瘤-癌序列的进展伴随着Ley和MUC1抗原的增加以及所有Lewis抗原的增加。另一方面,粘液癌表现出相反的模式。总之,这些结果表明,Ley和MUC1的免疫反应性与结肠肿瘤的恶性转化有关,而MUC2则是低级别不典型增生和粘液癌亚型的标志。
Previous studies on the immunoreactivity of various mucin peptide and carbohydrate antigens in neoplastic colorectal tissues led to at least in part contradictory results. Therefore, we investigated a series of 42 adenomas and 44 carcinomas applying monoclonal antibodies (mabs) directed against Lewis blood group antigens (sialyl-Le(a), Le(x), sialyl-Le(x), Le(y)) as well as mucin peptide cores (MUC1, MUC2 and MUC5AC) by immunohistochemistry. A statistically significant positive correlation between the development of high-grade dysplasia in colorectal adenomas and the immunoreactivity of Ley and MUC1 epitopes was observed, whereas MUC2 exhibited a significant negative correlation. The reactivity of the other epitopes did not show an association with the progression of malignant transformation. Colorectal carcinomas were subdivided according to their histopathological subtype. The immunohistochemical staining resulted in a significantly stronger MUC2 reactivity of mucinous vs. tubular adenocarcinomas. Immunoreactivity of the MUC1-specific mab, which does not react with the fully glycosylated peptide core, showed a statistically nonsignificant inverse tendency, whereas all carbohydrate antigens displayed a strong expression in both tumor subtypes. Furthermore, correlations between mucin peptide and carbohydrate epitope labelling were evaluated. Progression of the adenoma-carcinoma sequence was accompanied by an increase of Ley as well as MUC1 antigen and an increase of all Lewis antigens compared to MUC2 immunoreactivity. On the other hand, mucinous carcinomas exhibited an inverse pattern. In conclusion, these results demonstrate that Ley and MUC1 immunoreactivity correlate with malignant transformation in the colorecturn, whereas MUC2 represents a marker for low-grade dysplasia and the subtype of mucinous carcinomas.