Myerscough N, Sylvester P A, Warren B F, Biddolph S, Durdey P, Thomas M G, Carlstedt I, Corfield A P
University Department of Medicine, Bristol Royal Infirmary, Bristol, BS2 8HW, UK.
Glycoconj J. 2001 Nov-Dec;18(11-12):907-14. doi: 10.1023/a:1022204626604.
Anti-mucin variable number tandem repeat (VNTR) antibodies have been used previously to demonstrate the de novo presence of MUC5AC and MUC6 mucin in colorectal adenomas and increased synthesis of MUC2, the major secreted mucin in normal colorectal mucosa. Here we examined secreted mucins in tubular, tubulovillous and villous adenomas of the rectum using non-VNTR antibodies designed to assess mature mucin. Mucin gene messenger RNAs were detected by in situ hybridization. The anti-MUC2 non-VNTR antibody in the goblet cells of adenomas revealed a staining pattern of increased cytoplasmic, Golgi and membrane staining with no change in goblet vesicle reactivity compared with normal controls. In addition, blank goblet cell vesicle immunostaining for MUC2 was found in the transitional mucosa adjacent to all types of adenoma. Although a trend to overexpression of MUC2 was observed with in situ hybridization this was not detected with immunohistology. De novo synthesis of MUC5AC, but not MUC5B or MUC6 mucin was seen in all adenomas and transitional mucosa using immunohistochemistry. There was no correlation of MUC2 or MUC5AC mucin with polyp size or the grade of dysplasia using the non-VNTR antibodies. This study demonstrates that anti-mucin non-VNTR antibodies reveal a different subcellular-localization in rectal adenomas compared with normal colorectal mucosa. Further, this pattern is in contrast to that reported for anti-mucin VNTR antibodies. Combined use of these reagents may benefit future assessment of these cancers.
抗粘蛋白可变数目串联重复序列(VNTR)抗体此前已被用于证明结直肠腺瘤中MUC5AC和MUC6粘蛋白的新生存在,以及正常结直肠黏膜中主要分泌性粘蛋白MUC2合成的增加。在此,我们使用旨在评估成熟粘蛋白的非VNTR抗体,检测了直肠管状、管状绒毛状和绒毛状腺瘤中的分泌性粘蛋白。通过原位杂交检测粘蛋白基因信使核糖核酸。腺瘤杯状细胞中的抗MUC2非VNTR抗体显示,与正常对照相比,细胞质、高尔基体和膜染色增加,杯状小泡反应性无变化。此外,在所有类型腺瘤相邻的移行黏膜中发现了MUC2的空白杯状细胞小泡免疫染色。尽管原位杂交观察到MUC2有过表达趋势,但免疫组织化学未检测到。使用免疫组织化学在所有腺瘤和移行黏膜中均可见MUC5AC的新生合成,但未见到MUC5B或MUC6粘蛋白的新生合成。使用非VNTR抗体时,MUC2或MUC5AC粘蛋白与息肉大小或发育异常程度无相关性。本研究表明,与正常结直肠黏膜相比,抗粘蛋白非VNTR抗体在直肠腺瘤中显示出不同的亚细胞定位。此外,这种模式与抗粘蛋白VNTR抗体报道的模式相反。联合使用这些试剂可能有利于未来对这些癌症的评估。