Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands; Department of Oral, Maxillofacial Surgery Oral Pathology, VU University medical center and Academic Centre for Dentistry Amsterdam, Amsterdam, The Netherlands; Department of Pathology, VU University medical center, Amsterdam, The Netherlands.
Department of Pathology, VU University medical center, Amsterdam, The Netherlands.
Arch Oral Biol. 2017 Oct;82:121-126. doi: 10.1016/j.archoralbio.2017.06.010. Epub 2017 Jun 13.
The aberrant expression of mucins and mucin-type carbohydrates has been described in many types of cancer, including mucoepidermoid carcinoma (MEC), a malignant salivary gland tumor. In this study, we examined the aberrant expression patterns of mucins (MUC1, MUC4, MUC5AC and MUC5B), simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) and mature carbohydrate antigens (Lewis and sulfo-Lewis antigens) in MEC originating from the parotid gland, which normally does not secrete mucins.
We conducted an immunohistochemical study to investigate the presence of mucins and carbohydrates in 24 MEC samples originating from the parotid gland and in surrounding normal tissue of the same gland in comparison 6 samples of normal salivary glands. The expression levels were compared with respect to the histological grading. Furthermore, 24 MEC samples from non-parotid salivary glands were included.
We observed loss of topology of membrane-bound MUC1 and MUC4, and de novo expression of MUC5AC, MUC5B and sialyl-Tn in MEC that originated in the parotid gland. Furthermore, mucins MUC1, MUC4 and carbohydrate antigens Tn, sialyl-Tn, T, Lewis and sulfo-Lewis were overexpressed in MEC samples compared to surrounding normal salivary gland tissues. MUC1 was expressed in both low- and high grade MECs, whereas MUC4 was not expressed in high grade MECs of the parotid gland.
During the development of MEC in the parotid gland, the genes for gel-forming secretory mucins are switched on. Besides these MEC tissues overexpress short oligosaccharides, suggesting that the glycosylation machinery is altered.
黏蛋白和黏蛋白型碳水化合物的异常表达已在多种类型的癌症中被描述，包括黏液表皮样癌（MEC），一种恶性涎腺肿瘤。在这项研究中，我们检查了源自腮腺的 MEC 中黏蛋白（MUC1、MUC4、MUC5AC 和 MUC5B）、简单黏蛋白型碳水化合物抗原（Tn、唾液酸化-Tn 和 T）和成熟碳水化合物抗原（Lewis 和硫酸-Lewis 抗原）的异常表达模式，而腮腺通常不分泌黏蛋白。
我们进行了免疫组织化学研究，以调查源自腮腺的 24 例 MEC 样本和同一腺体周围正常组织中黏蛋白和碳水化合物的存在，并与 6 例正常涎腺样本进行比较。根据组织学分级比较了表达水平。此外，还纳入了 24 例来自非腮腺涎腺的 MEC 样本。
我们观察到源自腮腺的 MEC 中膜结合型 MUC1 和 MUC4 的拓扑结构丧失，以及 MUC5AC、MUC5B 和唾液酸化-Tn 的新表达。此外，与周围正常涎腺组织相比，MEC 样本中黏蛋白 MUC1、MUC4 和碳水化合物抗原 Tn、唾液酸化-Tn、T、Lewis 和硫酸-Lewis 过表达。MUC1 在低级别和高级别 MEC 中均有表达，而 MUC4 则在腮腺高级别 MEC 中不表达。
在腮腺 MEC 的发展过程中，凝胶形成分泌型黏蛋白的基因被激活。除了这些 MEC 组织过度表达短寡糖外，还表明糖基化机制发生了改变。
