Immunohistochemical Features of Intestinal and Foveolar Dysplasia in Barrett's Esophagus
Agoston T Agoston, Robert D Odze, Gregory Y Lauwers, Amitabh Srivastava. Brigham & Women's Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA
Background: Recently, two major subtypes of dysplasia in Barrett's Esophagus (BE) have been identified, termed “intestinal” (INT) or “gastric”, also referred to as “foveolar” (FOV). Some patients show a mixture of both types. Previous data have shown that these two subtypes of dysplasia may have different biological characteristics, arise from different types of BE mucosa, and may have different natural history and risk of malignancy. The aim of this study was to determine the immunohistochemical characteristics of these dysplasia subtypes in BE, with emphasis on the type of differentiation (intestinal vs. gastric) present in both.
Design: Thirty-eight BE-related endoscopic mucosal resections (EMR) were evaluated morphologically for the highest grade (low, high) and type of dysplasia (INT, FOV, mixed) by routine H&E histologic methods. Immunohistochemistry was performed for intestinal markers (CDX2, MUC2, and villin) and gastric markers (MUC5AC, MUC6) and for Ki67 and P53, and all markers were scored for the presence and degree of staining in a semiquantitative fashion (grade 0=negative, 1=focal, 2=multifocal, 3=diffuse staining). Staining was compared between the different types of morphologic dysplasia.
Results: By morphology, 11 (29%) were considered intestinal, 8 (21%) foveolar, and 16 (42%) mixed dysplasia. By immunohistochemistry, morphologically classified INT dysplasia showed significantly higher expression of INT markers, such as MUC2, CDX2, and villin, whereas FOV dysplasia showed significantly more MUC5AC and MUC6 expression. Mixed INT/FOV dysplasia showed an immunophenotypic pattern that matched, roughly, the morphologic areas of INT and FOV dysplasia. No significant differences were observed in P53 or Ki67 proliferative index. Interestingly, despite differences in quantity of the various INT and gastric immunomarkers in INT and FOV dysplasia, respectively, all cases of both types of dysplasia showed at least focal CDX2 staining.
Conclusions: Regardless of the morphologic phenotype of dysplasia, whether INT or FOV, all dysplastic epithelium shows some evidence of intestinalization characterized by at least focal CDX2 staining, similar to the background non-dysplastic metaplastic columnar epithelium as previously reported. In general, INT dysplasia shows more advanced INT immunophenotype, in contrast to FOV dysplasia which shows a more advanced gastric phenotype. Further studies are needed to determine whether dysplasia types with more advanced INT versus gastric differentiation have a different risk of malignancy.
Tuesday, March 20, 2012 11:45 AM
Platform Session: Section D, Tuesday Morning