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microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence

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World Journal of Gastroenterology 2008年第25期14卷 4070-4076页

作者： Jian-Chun Cai Di Liu Kai-Hua Liu Hai-Ping Zhang Shan Zhong Ning-Sao Xia Department of Oncology Surgery Xiamen Cancer Center Affiliated Xiamen First Hospital Fujian Medical University Xiamen 361003 Fujian Province China Department of Material Science andEngineering Chemistry and Chemical Engineering CollegeXiamen University Xiamen 361005 Fujian Province China National Institute of Diagnostics and VaccineDevelopment in Infectious Diseases Xiamen UniversityXiamen 361005 Fujian Province China

AIM: To investigate the microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence. METHODS: Forty-one specimens were obtained from esophageal cancer (EC) patients. Histopathological assessment identified 23 squamous cell carcinomas (SCC) and 18 adenocarcinomas (ADC), including only 8 ADC with Barrett esophageal columnar epithelium (metaplasia) and dysplasia adjacent to ADC. Paraffin-embedded normal squamous epithelium, Barrett esophageal columnar epithelium (metaplasia), dysplasia and esophageal tumor tissues were dissected from the surrounding tissues under microscopic guidance. DNA was extracted using proteinase K digestion buffer, and DNA was diluted at 1:100, 1:1000, 1:5000, 1:10 000 and 1:50 000, respectively. Seven microsatellite markers (D2S123, D3S1616, D3S1300, D5S346, D17S787, D18S58 and BATRII loci) were used in this study. Un-dilution and dilution polymerase chainreactions (PCR) were performed, and microsatellite analysis was carried out. RESULTS: No statistically significant difference was found in microsatellite instability (MSI) and loss of heterozygosity (LOH) of un-diluted DNA between SCC and ADC. The levels of MSI and LOH were high in the metaplasia-dysplasia-adenocarcinoma sequence of diluted DNA. The more the diluted DNA was, the higher the rates of MSI and LOH were at the above 7 loci, especially at D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci. CONCLUSION: The sequence of metaplasia-dysplasia-adenocarcinoma is associated with microsatellite alterations, including MSI and LOH. The MSI and LOH may be the early genetic events during esophageal carcinogenesis, and genetic alterations at the D3S1616, D5S346 and D3S123 loci may play a role in the progress of microsatellite alterations.

关键词： microsatellite alterlaons Dilution PCR Metaplasia-dysplasia-adenocarcinoma sequence Esophageal squamous epithelium Squamous cellcarcinoma

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