Foveolar type dysplasia in Barrett esophagus.
Adenocarcinoma of the lower esophagus and esophagogastric junction is increasing in incidence in Western countries. A metaplasia (Barrett esophagus)-dysplasia-carcinoma sequence induced by gastroesophageal reflux disease is established. Two patterns of Barrett dysplasias have been described-adenomatous (type 1) and non-adenomatous (type 2 or foveolar/hyperplastic type). Interestingly, little is known about non-adenomatous dysplasia. Esophagogastrectomy cases from 41 patients with glandular dysplasia with and without associated invasive adenocarcinoma of the lower esophagus were evaluated for expression of MUC2, MUC5AC, CDX2, villin, Ki67 and p53. Results were correlated with sub-classification of the dysplasia into morphologic patterns of adenomatous vs foveolar vs hybrid type. In addition, clinicopathological parameters including the presence and extent of background intestinal metaplasia were also evaluated. Foveolar type dysplasia was present in 46% of the cases and thus, was more common than adenomatous type or hybrid type (both approximately 27%) dysplasia. Immunohistochemistry confirmed the histological stratification in all cases. Foveolar type dysplasia commonly expressed MUC5AC (P<0.12) but was consistently negative for markers of intestinal differentiation, MUC2, CDX2 and villin (all P<0.01). By contrast, adenomatous type dysplasia frequently displayed intestinal differentiation markers (all P<0.0001) Hybrid-type dysplasia was similar to adenomatous type dysplasia in showing expression of intestinal differentiation markers (P<0.01) and therefore could not be sustained as a separate category. In conclusion, our study provides evidence for a non intestinal pathway to neoplastic development in Barrett esophagus, that is, gastric metaplasia-foveolar dysplasia-adenocarcinoma.
Brown
Ian S
IS
Department of Histopathology, Sullivan Nicolaides Pathology and Royal Brisbane and Women's Hospital Brisbane, Brisbane, Australia. ian_brown@snp.com.au
Whiteman
David C
DC
Lauwers
Gregory Y
GY
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology*; D000236:Adenoma / Q000737:chemistry / Q000473:pathology*; D000368:Aged; D001471:Barrett Esophagus / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000473:pathology*; D004947:Esophagus / Q000737:chemistry / Q000473:pathology*; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008679:Metaplasia; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D055271:Mucin 5AC / Q000032:analysis; D055262:Mucin-2 / Q000032:analysis; D011230:Precancerous Conditions / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D008840:Microfilament Proteins; D055271:Mucin 5AC; D055262:Mucin-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C026615:villin