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AIM To examine the fetal and neonatal esophagogastric junction region (EGJ) histologically for the presence of an equivalent to adult cardiac mucosa (CM); to study the expression patts of all cytokeratins (CK) relevant to the EGJ during gestation; to compare the CK profile of the gestational and the adult EGJ; and to determine the degree of development in the adult EGJ histology and CK profile during gestation.METHODS: Forty-eight fetal autopsy specimens of the EGJ were step-sectioned and stained with hematoxylin and eosin (H&E) to select sections showing the mucosal lining. Immunohistochemistry for CK5, 7, 8, 13, 18, 19,and 20 was performed. Antibody staining was then graded for location, intensity, and degree.RESULTS: The distal esophagus was lined by simple columnar epithelium from 12-wk gestational age (GA).The proximal part of this segment consisted of mucusproducing epithelium, devoid of parietal cells. CK5 and 13 were present exclusively in multilayered epithelia and CK8,18, and 19 predominantly in simple columnar epithelium.There were no differences in the frequencies of the coordinate CK7+/20+ and the CK7-/20- immunophenotypes between different locations. The prevalence of the CK7+/20- immunophenotype decreased, and that of the CK7-/20+ immunophenotype increased significantly from the distal esophagus to the distal stomach.CONCLUSION: Fetal columnar-lined lower esophagus (fetal CLE) may be the equivalent and precursor of the short segments of columnar epithelium found in the distal esophagus of some normal adult subjects. Esophageal simple columnar epithelium without parietal cells (ESN) may be the precursor of adult CM. The similarities between the fetal and adult EGJ and stomach CK expression patts support the conclusion that adult CM has an identifiable precursor in the fetus. This would then indicate that at least a part of the adult CM has a congenital origin.