Mandel U, Petersen O W, Sørensen H, Vedtofte P, Hakomori S, Clausen H, Dabelsteen E
Department of Oral Diagnosis, University Hospital, Copenhagen, Denmark.
J Invest Dermatol. 1991 Oct;97(4):713-21. doi: 10.1111/1523-1747.ep12484064.
Simple mucin-type carbohydrate antigens, T, Tn, and sialosyl-Tn, have been found to be good markers of malignant transformation in several epithelial tissues as a result of incomplete synthesis with precursor accumulation. The T, Tn, and sialosyl-Tn antigens represent the initial, most immature glycosylation of serine and threonine amino acids of proteins. In normal adult cells these structures are generally masked by addition of further saccharides to form more complex structures. We analyzed simple mucin-type carbohydrates in human labial stratified squamous and minor salivary gland epithelia in order to define the glycosylation pattern in normal cells in relation to epithelial differentiation and maturation. A panel of monoclonal antibodies with well-characterized specificity for T, Tn, sialosyl-Tn and the histo-blood group H and A variants hereof were used in immunohistology of sections from 30 individuals with known ABO, Lewis, and secretor status. In stratified epithelium the sialylated T structure was confined to cell membranes of immature basal cells, whereas the H and A variants were observed on cell membranes of more mature parabasal and spinous cell layers. Furthermore, superficial spinous cells produced a fine granular cytoplasmic staining for Tn and sialosyl-Tn antigens. In minor salivary glands mucous cells expressed Tn and sialosyl-Tn as well as the H and A variants in the area of the nucleus, whereas T and the H variant were found in duct cells and unsubstituted T antigen in myoepithelial cells. These results indicate that incomplete synthesis, i.e., deletion of sialyltransferases and/or histo-blood group ABH transferases, may result in accumulation of T, Tn, and sialosyl-Tn antigens in oral epithelia, thus offering a baseline for further studies of changes in premalignant and malignant oral epithelia.
简单粘蛋白型碳水化合物抗原T、Tn和唾液酸基Tn，已被发现是几种上皮组织恶性转化的良好标志物，这是由于合成不完全导致前体积累所致。T、Tn和唾液酸基Tn抗原代表蛋白质中丝氨酸和苏氨酸氨基酸最初、最不成熟的糖基化。在正常成年细胞中，这些结构通常会通过添加更多糖类形成更复杂的结构而被掩盖。我们分析了人唇分层鳞状上皮和小唾液腺上皮中的简单粘蛋白型碳水化合物，以确定正常细胞中与上皮分化和成熟相关的糖基化模式。一组对T、Tn、唾液酸基Tn以及组织血型H及其A变体具有明确特异性的单克隆抗体，用于对30名已知ABO、Lewis和分泌状态个体的切片进行免疫组织化学研究。在分层上皮中，唾液酸化T结构局限于未成熟基底细胞的细胞膜，而H和A变体则出现在更成熟的基底旁细胞层和棘细胞层的细胞膜上。此外，表层棘细胞对Tn和唾液酸基Tn抗原产生细颗粒状胞质染色。在小唾液腺中，粘液细胞在细胞核区域表达Tn和唾液酸基Tn以及H和A变体，而T和H变体则在导管细胞中发现，肌上皮细胞中发现未取代的T抗原。这些结果表明，合成不完全，即唾液酸转移酶和/或组织血型ABH转移酶的缺失，可能导致口腔上皮中T、Tn和唾液酸基Tn抗原的积累，从而为进一步研究癌前和恶性口腔上皮的变化提供了基线。
