[680] Utility of Lethal Giant Larva-2 (Lgl2) Gene Expression and MUC Proteins in Distinguishing Barrett's Gastric-Type Dysplasia from Reactive Gastric Cardiac Mucosa in GERD.

Deepa T Patil, Ana E Bennett, Dipti Mahajan, Mary P Bronner. Cleveland Clinic

Background: Barrett's gastric-type dysplasia is characterized by non-stratified, basally oriented but enlarged nuclei with mild pleomorphism. Nuclear stratification and surface predominant atypia with non-crowded, villiform architecture are features that most reliably distinguish marked reactive cardiac atypia in GERD from gastric-type Barrett's dysplasia on histology {Patil D 2010}. Recent reports demonstrate that Lgl2, a Drosophila gene with a putative tumor-suppressor function in mammals, is either aberrantly expressed or lost in gastric dysplasia and adenocarcinoma and retained in reactive gastric mucosa. We sought to evaluate the utility of Lgl2, MUC2, MUC5AC and MUC6 proteins in separating Barrett's gastric-type dysplasia from reactive cardia in GERD.
Design: A total of 3,698 biopsies from 461 Barrett's patients were reviewed to identify 43 patients (80 biopsies) with Barrett's gastric-type dysplasia (13 LGD,30 HGD) using previously defined criteria. These were compared to biopsies from 60 GERD patients with markedly inflamed and reactive cardiac mucosa. Ten cases from each cohort were immunostained for Lgl2 and the pattern (basolateral membranous, cytoplasmic) and intensity of staining were scored. Cytoplasmic expression or apical membrane staining was considered aberrant expression. Cytoplasmic expression was considered as positive staining for MUC2, MUC5AC and MUC6.
Results: Moderate to strong basolateral membranous staining of the surface epithelial cells was seen in all cases of reactive cardia in GERD (100%). In contrast, 8/10 (90%) cases of Barrett's gastric-type dysplasia showed either no Lgl2 expression or weak cytoplasmic expression (1/10;p=0.03). Strong MUC5AC expression in the surface epithelium but not in the deeper glands was seen in all cases of reactive cardia and Barrett's dysplasia. The opposite staining pattern was noted with MUC6 in that 8/10 (80%) cases of reactive cardia and 9/10 (90%) cases of Barrett's dysplasia revealed strong expression in the deep glands only. Only 10% of reactive cardia (1/10) versus 90% of Barrett's dysplasia (9/10) showed MUC2 expression in 5%-50% of the epithelial cells (p=0.011).
Conclusions: Loss or aberrant Lgl2 and gain of MUC2 expression are useful adjunct tools to differentiate Barrett's gastric-type dysplasia from reactive cardiac atypia in GERD. The complementary staining patterns of MUC5AC and MUC6 in the superficial and deep glands confirm the gastric phenotype of Barrett's dysplastic epithelium; however, does not differentiate reactive cardia from Barrett's gastric-type dysplasia.
Category: Gastrointestinal

Monday, February 28, 2011 1:00 PM

Poster Session II # 83, Monday Afternoon

 

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