Abnormal subcellular distribution of mature MUC2 and de novo MUC5AC mucins in adenomas of the rectum: immunohistochemical detection using non-VNTR antibodies to MUC2 and MUC5AC peptide.
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.
Myerscough
N
N
University Department of Medicine, Bristol Royal Infirmary, Bristol, BS2 8HW, UK.
Sylvester
P A
PA
Warren
B F
BF
Biddolph
S
S
Durdey
P
P
Thomas
M G
MG
Carlstedt
I
I
Corfield
A P
AP
D000236:Adenoma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D014408:Biomarkers, Tumor; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D006801:Humans; D007106:Immune Sera; D007150:Immunohistochemistry / Q000379:methods*; D018598:Minisatellite Repeats / Q000276:immunology; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012004:Rectal Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013347:Subcellular Fractions; D014158:Transcription, Genetic
D000906:Antibodies; D014408:Biomarkers, Tumor; D007106:Immune Sera; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; D009363:Neoplasm Proteins; D010455:Peptides; D012333:RNA, Messenger