Primary Motility  Disorders of the  Esophagus
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Volume: Barrett's Esophagus
Chapter: Short Barrett's esophagus

In patients with junctional type mucosa at the esophagogastric junction, could the use of monoclonal antibodies allow for previsions of further development of specialized epithelium?

L.H. Griffel, P.S. Amenta, K.M. Das (New Brunswick)

Barrett's esophagus is a condition of columnar metaplasia of the esophagus that was first described by Norman Barrett in 1950 [1]. Since that time, the definition of this condition has undergone numerous changes. Initially thought to be a congenitally shortened esophagus, work by Allison and Johnstone [2] showed that the condition did indeed involve columnar metaplasia of the esophagus. For the next forty-odd years, any columnar metaplasia of the esophagus was considered to be Barrett's esophagus whether it was fundus, cardia/junctional or intestinal type mucosa. In the 1990's the incidence of adenocarcinoma of the esophagus was noted to be rapidly rising faster than the rate of any other cancer [3-5]. This cancer is highly associated with intestinal metaplasia (IM) of the esophagus and thus the definition of Barrett's esophagus has evolved to include only intestinal metaplasia of the esophagus or more specifically "specialized columnar epithelium" [6].

Despite screening of patients with specialized columnar epithelium, the rate of esophageal cancer continues to rise. This has lead one to wonder if we are screening the right group of patients. Whereas specialized columnar epithelium is the type that is associated with adenocarcinoma, the developmental process of going from squamous epithelium to specialized columnar epithelium is poorly understood. Recent work by Chandrasoma and Oberg has suggested that cardia type epithelium is abnormal, even when found in the stomach, and represents a metaplastic process in response to reflux disease [7, 8]. This led us to further investigate the phenotype of cardia (or junctional) type epithelium of the esophagus.

We have previously reported that the monoclonal antibody mAbDAS-1 (formerly known as 7E12H12) reacts both sensitively and specifically with Barrett's epithelium (specialized columnar epithelium), but not with normal esophagus, including esophagitis, stomach or small intestinal [9]. Given the fact that this antibody was developed against a colonic epitope [10] and that it does not react at all with small bowel, we presume that the antibody reacts only with incomplete, or colonic type IM. This is further supported by the fact that the antibody reacts with approximately 25% of gastric IM, which is roughly the percentage that is felt to be incomplete type [11]. This is also the type of gastric IM that is at risk of developing into adenocarcinoma. This is further supported by our recent observation that 95% of patients with gastric IM associated with gastric carcinoma reacted with mAbDAS-1 [12].

We have recently reported that this antibody reacts with approximately one-third of cases of junctional or cardia type of epithelium when this epithelium is found within the tubular esophagus, but it does not react with epithelium from the gastric cardia [13]. This has also been shown in collaborative work that we have done with a group in the Netherlands [14]. In that series we found that approximately 40% of patients with cardia type mucosa at the gastroesophageal junction exhibited reactivity with the antibody out of a large number of patients (201 of 486 patients).

These facts suggest that cardia (or junctional) type epithelium is indeed metaplastic and may represent an intermediate phase in the development of IM. We have reported of a few instances where initial endoscopic biopsy revealed a cardia type epithelium of the esophagus, which exhibited reactivity with mAbDAS-1, and on subsequent exam the patient did develop IM [15]. We have also examined whether this reactivity is with early goblet cell components not visible with light microscopy by staining parallel sections with a goblet cell specific antibody and found that that was not the case [16]. Biopsy specimens from the cardia in these patients have routinely been non-reactive with mAbDAS-1. In total, we have examined over 150 samples of gastric cardia from patients who also had their distal esophagus biopsied and only 14 have shown mAbDAS-1 reactivity. Of these 14, 9 were from patients who had cardia/junctional epithelium in the distal esophagus that also reacted with the antibody.

We have looked at alcian blue reactivity in parallel and found that in almost all of the cardia/junctional type epithelium specimens, there are some areas with a blue blush type alcian blue positivity. This reactivity represents the presence of acid mucin. The monoclonal antibody reacts with a colonic protein and not with enterocytes or goblet cells. As mAbDAS-1 does not react with any epithelium of the gastrointestinal tract other than colon or Barrett's epithelium, it suggests that alcian blue and the antibody are not identifying the same thing and that the antibody more specifically identifies colonic metaplasia.

Given all of our experience and work by several other independent investigators using the mAbDAS-1 antibody we feel that junctional type mucosa at the esophagogastric junction represents a dynamic process with metaplastic change and may be a precursor to the development of specialized columnar epithelium. Further work is necessary to identify those patients at highest risk for developing specialized columnar epithelium.


1. Barrett NR. Chronic peptic ulcer of the oesophagus and "oesophagitis". Brit J Surg 1950;38:175-182.

2. Allison PR, Johnstone AS. The oesophagus lined with gastric mucous membrane. Thorax 1953;8:87-101.

3. Haggitt RC. Adenocarcinoma in Barrett's esophagus: a new epidemic? Hum Pathol 1992;123:475-476.

4. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265:1287-1289.

5. Potet F. Le cancer du cardia et le cancer sur endobrachyoesophage sont-ils des entités différentes? Goastroenterol Clin Biol 1994;18:D56-D58.

6. Sampliner RE, and The Practice Parameters Committee of The American College of Gastroenterology. Practice guidelines on the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastroenterol 1998;93:1028-1032.

7. Chandrasoma PT. Pathology of Barrett's esophagus. Semin Thorac Cardiovasc Surg 1997;9:270-278.

8. Oberg S, Peters JH, DeMeester TR, Chandrasoma P, Hagen JA, Ireland AP, Ritter MP, Mason RJ, Crookes P, Bremmer CG. Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease. Ann Surg 1997;226:522-532.

9. Das KM, Prasad I, Garla S, Amenta P. Specialized Barrett's epithelium shares a colon epithelial epitope as detected by a novel monoclonal antibody. Ann Intern Med 1994;120:753-756.

10. Das KM, Sakamaki S, Vecchi M, Diamond B. The production and characterization of monoclonal antibodies to a human colonic antigen associated with ulcerative colitis:cellular localization of the antigen using the monoclonal antibody. J Immunol 1987;139:77-84.

11. Hirota T, Okada T, Habishi M, Kitaika H. Significance of intestinal metaplasia as a precancerous lesion of the stomach. In: Ming SC, ed. Precursors of gastric cancer. New York: Praeger, 1984:179-193.

12. Das KM, Slate JA, Ramsundar L, Amenta PS, Prasad S, Yokota K, Tanabe H, Sato T, Kohgo Y. Gastric intestinal metaplasia with colonic phenotype, as detected by a novel biomarker mAbDAS-1, is highly associated with gastric carcinoma. Gastroenterology 2000;118:A273.

13. Griffel LH, Amenta PS, Das KM. Use of a novel monoclonal antibody in diagnosis of Barrett's esophagus. Dig Dis Sci 2000:45(1):40-48.

14. Wolf C, Seldenrijk CA, Das KM, Timmer R, Breumelhof R, Smout AJPM, Amenta PS, Griffel LH. Prevalence of mAb DAS-1 positivity in biopsies from the esophagogastric junction. Gastroenterology 2000;118:A1324.

15. Griffel LH, Weston AP, Karalnik NA, Amenta PS, Das KM. Early diagnosis of short segment Barrett's esophagus (SSBE) using an immunohistochemical marker: an interinstitutional study. Gastroenterology 1998;114:A140.

16. Griffel LH, Karalnik NA, Weston AP, Mohan V, Amenta PS and Das KM. Cellular phenotype of " cardia type" Barrett's epithelium (BE). Gastroenterology 1999;116:A177.

Publication date: August 2003 OESO©2015