Early genetic instability of both epithelial and stromal cells in esophageal squamous cell carcinomas, contrasted with Barrett's adenocarcinomas |
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Authors: | Hiroaki Shiraishi Tetuo Mikami Tsutomu Yoshida Satoshi Tanabe Nobuyuki Kobayashi Masahiko Watanabe Isao Okayasu |
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Institution: | (1) Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara 228-8555, Japan;(2) Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan;(3) Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan |
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Abstract: | Background We have shown previously that stromal genetic alteration may make a greater contribution to early genesis of ulcerative colitis-associated
tumors than sporadic colon cancers. We assessed whether similar differences in genetic alteration might exist between squamous
cell carcinomas (SCCs) and Barrett's adenocarcinomas (BACs) of the esophagus.
Methods We investigated epithelial and stromal genetic instability with five National Cancer Institute standard (NCI), four chromosome
17 (Chr. 17), and six tumor suppressor gene (TSG) microsatellite markers in 26 SCC and 12 BAC cases and in 11 normal controls,
using a novel combination of microdissection, polymerase chain reaction, and GeneScan.
Results Frequency of epithelial loss of heterozygosity (LOH) increased in the order background mucosa, to precursor lesions, to tumors
with both types of carcinoma, especially for the Chr. 17 and TSG markers, while stromal LOH was relatively high but consistent
from background mucosa to carcinoma. Epithelial LOH of D17S796 demonstrated a significantly higher frequency in SCCs than
in BACs, without significant variation in p53 overexpression. The frequency of microsatellite instability (MSI) showed constant
high levels in both epithelium and stroma of background, dysplasia, and carcinomas in the SCC series, and rather low frequencies
in the BAC series. Although epithelial hMLH1 and hMSH2 expression decreased with tumor progression, no correlation was found
with the individual MSI status.
Conclusions Although epithelial LOH exists similarly in both lesion types, whereas epithelial and stromal MSI may occur in a relatively
early phase of SCC development, stromal MSI is rare in BACs, strongly suggesting differences in tumorigenesis between the
two types. |
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Keywords: | esophageal cancer epithelium stroma LOH MSI |
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