Genetic Alterations in Barrett Esophagus and Adenocarcinomas of the Esophagus and Esophagogastric Junction Region Tsung-Teh Wu, Toshiaki Watanabe, Richard.

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Genetic Alterations in Barrett Esophagus and Adenocarcinomas of the Esophagus and Esophagogastric Junction Region Tsung-Teh Wu, Toshiaki Watanabe, Richard Heitmiller, Marianna Zahurak, Arlene A. Forastiere, Stanley R. Hamilton The American Journal of Pathology Volume 153, Issue 1, Pages 287-294 (July 1998) DOI: 10.1016/S0002-9440(10)65570-8 Copyright © 1998 American Society for Investigative Pathology Terms and Conditions

Figure 1 Allelic loss of chromosome 17p in the region of the p53tumor suppressor gene in adenocarcinoma (Ca) and high-grade columnar epithelial dysplasia (H) as compared with the control nonneoplastic esophageal mucosa (N) of the same patient. Allelic loss (arrow) is evidenced by the absence of one heterozygous band (D17S520) and a 50% decrease in intensity in two others (VNTR and D17S1176). The American Journal of Pathology 1998 153, 287-294DOI: (10.1016/S0002-9440(10)65570-8) Copyright © 1998 American Society for Investigative Pathology Terms and Conditions

Figure 2 Allelic loss of chromosome 18q in adenocarcinoma (Ca) and high-grade columnar epithelial dysplasia (H) as compared with control nonneoplastic esophageal mucosa (N) of the same patient. The adenocarcinoma showed complete loss of 18q (arrows), whereas the HGD had partial loss (D18S55, D18S61, and D18S58). The American Journal of Pathology 1998 153, 287-294DOI: (10.1016/S0002-9440(10)65570-8) Copyright © 1998 American Society for Investigative Pathology Terms and Conditions

Figure 3 RER in adenocarcinoma (Ca) with nondysplastic Barrett mucosa (B). Microsatellite instability in the adenocarcinoma is evidenced by the presence of additional bands (arrows) in the three microsatellite markers shown, but the Barrett mucosa is RER−. The American Journal of Pathology 1998 153, 287-294DOI: (10.1016/S0002-9440(10)65570-8) Copyright © 1998 American Society for Investigative Pathology Terms and Conditions

Figure 4 Accumulation of genetic alterations in the morphological dysplasia–adenocarcinoma sequence in the distal esophagus and EGJ region. B, non-dysplastic Barrett mucosa; LGD, low-grade columnar epithelial dysplasia; HGD, high-grade columnar epithelial dysplasia; CA-B, adenocarcinoma with Barrett mucosa; CA, adenocarcinoma without Barrett mucosa; IHC, immunohistochemical stain; RER+, DNA replication errors. All alterations were more common in adenocarcinoma and HGD than in nondysplastic Barrett mucosa. The American Journal of Pathology 1998 153, 287-294DOI: (10.1016/S0002-9440(10)65570-8) Copyright © 1998 American Society for Investigative Pathology Terms and Conditions

Figure 5 Multiple allelic losses of chromosomes 17p, 18q, and 5q. Multiple losses were common in high-grade columnar epithelial dysplasia (HGD), adenocarcinomas with Barrett mucosa (CA-B), and adenocarcinomas without Barrett mucosa (CA), but less frequent in low-grade columnar epithelial dysplasia (LGD) and nondysplastic Barrett mucosa (B). The American Journal of Pathology 1998 153, 287-294DOI: (10.1016/S0002-9440(10)65570-8) Copyright © 1998 American Society for Investigative Pathology Terms and Conditions

Figure 6 Kaplan-Meier survival curves of patients with adenocarcinoma in the distal esophagus and the EGJ region according to TNM stage (A) and allelic losses of chromosomes 17p and 18q (B). Survival was significantly better in patients with stage I disease than in patients with higher clinical stages. Allelic loss of 17p or 18q alone was marginally associated with survival (see Table 3). However, patients with allelic losses of both 17p and 18q in their cancers had significantly worse survival than patients with either one or no allelic loss (P = 0.002). The American Journal of Pathology 1998 153, 287-294DOI: (10.1016/S0002-9440(10)65570-8) Copyright © 1998 American Society for Investigative Pathology Terms and Conditions