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IMMUNOHISTOCHEMICAL DEMONSTRATION OF ESOPHAGEAL DILATED INTERCELLULAR SPACES (DIS) IN SQUAMOUS MUCOSA
RH Riddell1, S McDonald2, R White2, C Yang2, D Armstrong3
1Pathology & Lab Medicine, Mt Sinai Hospital, Toronto; 2AstraZeneca Canada Inc, Mississauga; 3McMaster University, Hamilton, ON
BACKGROUND: Criteria for the histological diagnosis of esophageal acid-related disease in squamous mucosa have been hampered by lack of sensitivity and specificity. The possibility that dilated intercellular spaces (DIS) might be a sensitive marker of gastro-esophageal reflux disease (GERD) and non-erosive reflux disease (NERD) has been suggested.
Design: To determine whether immunohistochemical stains might demonstrate DIS with greater ease than H and E sections, biopsies of squamous mucosa (two from the Z-line, two from 2cms above the Z-line, one from 8cm above the Z-line, and one from the most distal erosion if present), were examined in 50 patients with acid-related GI symptoms as part of a randomized control trial. All patients underwent endoscopy and biopsy from these sites both pre-therapy and after 6 months of therapy (esomeprazole 40mg od or 20mg od prn), and all biopsies were oriented on filter paper. Four immunostains (desmocollin2, desmoglein2, CD15 and b-catenin) were compared to standard HE sections and to each other. DIS were scored on a 0-3 grading system as 0, 1 or 2, 3-5 or >5 DIS/x63 hpf respectively. The highest score recorded was used in view of the potential focality of GERD.
RESULTS: DIS were preferentially located in the suprabasal and peripapillary region of the squamous mucosa. All immunostains identified slightly different areas of the squamous epithelium. b-catenin and desmoglein2 were best able to demonstrate DIS with ease and separate them from cytoplasmic vacuoles. They also showed the greatest differences in pre- and post-treatment biopsies regarding scoring of DIS, and correlated well with scores obtained with HE sections (all p values <.025).
CONCLUSIONS: b-catenin and desmoglein2 allowed the best demonstration of DIS as scored in both pre- and post-treatment biopsies of squamous mucosa in patients with acid-related disease. As b-catenin is more likely to be available in routine practice, and was less capricious, its use as a potential marker of DIS is suggested. This study also supports the evaluation of DIS as a marker in patients with acid-related disease that can be used at the light microscopic level.
This study was supported by AstraZeneca Canada Inc