Gastroenterology

Gastroenterology

Volume 122, Issue 3, March 2002, Pages 784-788
Gastroenterology

Case Reports
Molecular evidence for the same clonal origin of both components of an adenosquamous Barrett carcinoma

https://doi.org/10.1053/gast.2002.31903Get rights and content

Abstract

We describe an uncommon case of adenosquamous carcinoma arising in a Barrett esophagus in a 72-year-old white man who occasionally used alcohol, and was a nonsmoker for 34 years. Polymerase chain reaction–based microsatellite analysis was performed on the adenocarcinoma component (AC) and squamous cell carcinoma component (SC) of the tumor. The metaplastic Barrett epithelium (BE), the AC and the SC all showed loss of the same allele at 4 markers on chromosome 9p. Furthermore, the AC and the SC both showed loss of the same allele at all informative markers tested on chromosomal arms 3p, 5q, 10q, 14q, and 18q. In addition, both the SC and AC component contained the same missense mutation in the p53 tumor-suppressor gene. The only observed difference was a shift at a marker on chromosome 16q in the AC, whereas no shift was found in the BE and the SC. These findings suggest that this biphasic tumor has a monoclonal origin. The divergence presumably occurred late in the tumorigenesis of this carcinoma.

GASTROENTEROLOGY 2002;122:784-788

Section snippets

Case report

A 72-year-old white man presented with pyrosis and long-standing complaints of severe gastroesophageal reflux. He had no difficulty with food passage and had no weight loss. There was no history of smoking for the last 34 years and he occasionally used alcohol, on average 3 units per week. Physical examination was unremarkable, sedimentation rate was 6 mm/hour, and hemoglobin 9.4 mmol/L. At gastroscopy, Barrett mucosa over a length of 9 cm (29 to 38 cm from the incisors) and a hiatus hernia (38

Immunohistochemistry

Immunohistochemistry for cytokeratin (clone Cam 5.2; Becton Dickinson, San Jose, CA) and p53 (clone DO-7; Dako, Glostrup, Denmark) was performed using standard methods.

Microsatellite analysis

Formalin-fixed, paraffin-embedded tissue was available from normal lymphocytes, normal squamous cell epithelium (NSE), metaplastic Barrett epithelium (BE), invasive adenocarcinoma (AC), and squamous cell carcinoma (SC). Enrichment for metaplastic and tumor cells was achieved by careful microdissection. Microdissection for the AC

Results

Adenosquamous carcinoma of the esophagus is a very rare tumor with an obscure histogenesis. We describe a case of adenosquamous carcinoma in Barrett esophagus in a patient who occasionally used alcohol, but was a nonsmoker.

In this case, we used a molecular-genetic approach to characterize and to understand the histogenesis of this adenosquamous carcinoma arising in Barrett mucosa. Table 1 summarizes the results of the LOH and p53 sequence analysis for BE, AC, and SC.

The LOH on chromosomal arm

Discussion

The molecular alterations associated with adenocarcinoma and squamous cell carcinoma of the esophagus have been addressed in many recent studies and some of these studies have compared the molecular make-up of adenocarcinoma and squamous cell carcinoma. Our findings are in agreement with these studies; i.e., loss of the loci on chromosomal arms 3p, 5q, 9p, and 18q, as well as mutation of the p53 tumor-suppressor gene are frequently seen in both tumor types.10, 11 Surprisingly, adenocarcinoma

Acknowledgements

The authors thank Eric Caspers for excellent technical assistance.

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Address requests for reprints to: G. Johan A. Offerhaus, M. D., Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. e-mail: [email protected]; fax: (31) 20 696 0389.

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