Oncogene Expression and Amplification in Barrett Adenocarcinoma

• Published in: International journal of surgical pathology 1997-04, Vol.4 (4), p.203-211
• Main Authors: Gramlich, Terry L., Fritsch, Christine, Cohen, Cynthia, Samuel, Marsha, Hunt, Dirk, Dean, Patrick J., Gansler, Ted
• Format: Article
• Language: English
• ISSN: 1066-8969; 1940-2465
• DOI: 10.1177/106689699700400402

Oncogene activation by amplification and/or overexpression has been implicated in the development and progression of a number of malignancies. To better define the role of oncogene activation in adenocarcinomas arising in the setting of Barrett esophagus, we examined 44 resected Barrett adenocarcinomas for c-erb B-2, epidermal growth factor receptor (EGFR), c-myc, and cyclin DI gene amplification as well as c-erb B-2 and EGFR expression. DNA was extracted from formalin-fixed paraffin-embedded tissue and analyzed by differential polymerase chain reaction, a technique that permits semiquantitative analysis of gene dosage on archival material. Formalinfixed paraffin-embedded sections were stained with monoclonal antibodies directed against either the internal domain of c-erb B-2 or the extracellular domain of EGFR with a labeled streptavidin biotin technique. C-erb B-2 amplification was identified in three (7%) cases. A plasma membrane pattern of c-erb B-2 immunoreactivity in >50% of tumor cells correlated highly with c-erb B-2 amplification (P=.00008). EGFR amplification was noted in 18% of cases and correlated highly with the intensity of EGFR immunoreactivity (P=.0004). C-myc amplification was present in 18% of cases. No tumors showed cyclin DI amplification. Follow-up was available regarding 29 patients and showed decreased mean survival (P=.029) in patients with strong EGFR immunoreactivity (5.8 months) versus those with weak or absent EGFR labeling (11.8 months), and a trend toward decreased one-year survival (P=.069) for patients with (17%) versus those without (52%) c-myc amplification. Our results indicate one or more selected oncogenes are amplified/overexpressed in some Barrett adenocarcinomas and that EGFR and c-erb B-2 overexpression correlates with amplification. Additionally, strong EGFR expression in tumor cells indicates a poorer prognosis.