Mucin expression in reactive gastropathy: an immunohistochemical analysis.
BACKGROUND
Reactive gastropathy is the second most common diagnosis made on gastric biopsies. Increased epithelial proliferation and modifications of epithelial cytokeratin profile, distinct from those of Helicobacter pylori gastritis, have been previously reported. However, the evaluation of mucins, important components of the protective mucosal mucous layer, has not been reported.


OBJECTIVE
To investigate alterations of membrane and secreted mucins in reactive gastropathy of various etiologies using antibodies against mucin glycoproteins.


METHODS
Thirty-eight gastric biopsies diagnosed as reactive gastropathy, related to nonsteroidal anti-inflammatory drugs (n = 18) or bile reflux (n = 6) or of indeterminate etiology (n = 14), were evaluated using antibodies to MUC1, MUC5AC, MUC6, and MUC2. All cases were confirmed to be negative for H. pylori. The biopsies were classified in 3 groups based on the severity of cytoarchitectural changes (mild, moderate, and severe). Mucin expression and its distribution were recorded and the results correlated with the cytoarchitectural alterations and etiologies.


RESULTS
Loss of MUC1, either patchy or complete, was noted in 67% of the cases. Aberrant expression of MUC5AC in pyloric glands was observed in 81% of the cases, and aberrant expression of MUC6 in the upper foveolar epithelium was diffusely seen in 14% of the cases. Aberrant expression of MUC2 in non-goblet cells was observed in a single case. Aberrant expression of MUC6 was less extensive in the nonsteroidal anti-inflammatory drugs group than in other 2 groups (P = .03). Concurrently, the diffuse distribution of aberrant MUC6 expression was seen only in the cases of severe gastropathy (P = .09). There was no correlation between modifications in expression of other mucins and either the etiologies or the severity of cytoarchitectural changes.


CONCLUSIONS
Expressions of membrane (MUC1) and secreted (MUC5AC, MUC6) mucins are frequently modified in reactive gastropathy. The alteration of MUC1, which is involved in cell adhesion and polarity, may play a role in the development of the serrated profile of reactive gastropathy. Milder modifications of the secreted mucins may be explained by the reactive/regenerative nature of the process. Importantly, theses changes are different from the increase in MUC6 and reduction of MUC5AC expression reported in H. pylori gastritis, underlying their mechanistic differences. It is worth noting that similar alterations of mucin expression are shared by various etiologies, that is, nonsteroidal anti-inflammatory drugs and bile reflux, consistent with the nonspecific nature of reactive gastropathy.
Mino-Kenudson
Mari
M
Massachusetts General Hospital Department of Pathology, Boston, MA 02114-2696, USA.
Tomita
Shigeki
S
Lauwers
Gregory Y
GY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies / Q000032:analysis; D001706:Biopsy; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D018396:Mucin-1 / Q000276:immunology / Q000378:metabolism*; D055272:Mucin-6; D009077:Mucins / Q000276:immunology / Q000378:metabolism*; D013270:Stomach / Q000473:pathology; D013272:Stomach Diseases / Q000378:metabolism* / Q000473:pathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D055271:Mucin 5AC; D018396:Mucin-1; D055272:Mucin-6; D009077:Mucins