Is Barrett's Esophagus the Precursor of Most Adenocarcinomas of the Esophagus and Cardia? A Biochemical Study

Abstract

ObjectiveTo obtain biochemical evidence that Barrett's esophagus (BE) is the precursor of most adenocarcinomas (Adc) of the esophagus and cardia. Summary Background DataBased on morphologic data, BE was previously proposed as the precursor of most Adc of the esophagus. This hypothesis would receive strong support if biochemical evidence were found to demonstrate a pattern common to BE and Adc of the esophagus and cardia. MethodsWe studied the presence of intestinal-type proteins sucrase-isomaltase (SI) and crypt Cell Antigen (CCAg) in BE, Barrett's Adc, and esophageal-cardial Adc without BE. In each case specimens were collected from normal esophagus, stomach, tumor, and BE mucosa when present. To study related conditions, five specimens of peptic esophagitis and of squamous cell carcinoma were also analyzed. An indirect immunofluorescence technique was employed and sections were analyzed with laser confocal microscopy imaging. ResultsMost Barrett's mucosa specimens stained positively for SI (93%) and CCAg (89%). These proteins were detected in BE independently of the type of metaplasia, the coexistence of dysplasia, or the presence of associated Adc. SI and CCAg were present in 25 (96%) and 24 (92%) of the cases of Adc respectively. No statistical difference was detected in SI and CCAg expression between Adc samples with and without BE, between BE and Adc samples with or without BE, and between tumors located in the esophagus versus the cardia. No staining for these proteins was detected in stomach or esophageal mucosa, in submucosal glands of the esophagus, in peptic esophagitis or squamous cell carcinoma. ConclusionThese data show that BE and Adc of the esophagus and cardia have a similar phenotype and support the hypothesis that most of these tumors probably originate from preexisting BE. 725

Dendritic Cell-Associated Immune Inflammation of Cardiac Mucosa: A Possible Factor in the Formation of Barrett’s Esophagus

“…The importance of cardiac mucosa as the possible precursor lesion to Barrett's esophagus is indicated by studies showing similar protein expression profiles for both cardiac mucosa and Barrett's esophagus, including the expression of the small intestine marker proteins sucraseisomaltase and crypt cell antigen, and DAS-1, a marker of specialized columnar mucosa. [31][32][33][34] Compelling evidence has also been provided by studies that found cardiac mucosa developing in the cervical remnant esophagus after esophagectomy, an in vivo human model for de novo reflux disease. 3,35 In one such study, 35 intestinal metaplasia developed in some patients with adenocarcinoma subsequently arising in one protein expression features.…”

Preoperative chemotherapy unmasks underlying Barrett’s mucosa in patients with adenocarcinoma of the distal esophagus

“…In a study by Mendes de Almeida et al, the expression of the small intestinal proteins sucrase isomaltase (SI) and crypt cell antigen (CCAg) was evaluated in patients with Barrett's esophagus, in its putative precursor tissues, and in esophageal adenocarcinoma [8]. They did not ®nd a statistical dierence in SI and CCAg expression between specimens from adenocarcinoma with or without Barrett's tissue.…”

Immunohistochemical Markers for Barrett’s Esophagus and Associations to Esophageal Z-Line Appearance

“…Only staining in areas of IM was evaluated. Specimens were considered BE positive if they showed the speci c staining pattern as described earlier (12)(13)(14)(15)26) and were as follows: CK13, variable epithelial reactivity in both crypt-like and glandular cells; CK7, diffuse moderate to strong staining of both super cial and deep glands; CK20, band-like staining of surface epithelium and super cial glands; and CaCO3/73, predominantly expressed at the apical membrane.…”