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Mutational spectra of p53 in geographically localized esophageal squamous cell carcinoma groups in China
Author(s) -
Cao Wei,
Chen Xufeng,
Dai Huifang,
Wang Huizhen,
Shen Binghui,
Chu David,
McAfee Taylor,
Zhang ZuoFeng
Publication year - 2004
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20437
Subject(s) - transversion , incidence (geometry) , medicine , point mutation , exon , carcinoma , metastasis , immunohistochemistry , mutation , esophageal cancer , pathology , esophageal squamous cell carcinoma , cancer research , gene , cancer , oncology , biology , genetics , physics , optics
Abstract BACKGROUND Esophageal carcinoma is a particularly interesting tumor because of the dramatic difference in its incidence and geographic distribution among populations of similar ethnic origin. Epidemiologic data have suggested that many environmental exposures may be associated with an increased risk of its formation. METHODS In this study, 92 samples of esophageal squamous cell carcinoma (ESCC) were collected from patients who resided in 2 geographic areas in China with different incidences of ESCC: Linxian and Zhejiang. Overexpression and mutations of the p53 tumor‐suppressor gene were examined by using immunohistochemistry, single‐strand conformation polymorphism analysis, and direct sequencing. RESULTS The rates of point mutation and overexpression of p53 in the ESCC specimens studied were 30.4% (29 of 92 specimens) and 51.1% (47 of 92 specimens), respectively. The overexpression of p53 was associated with tumor metastasis and with 5‐year case fatality. Significant differences were found in the rates of overexpression and mutations in patients with clinical T2 tumors between the specimens from Linxian, which is a high‐incidence geographic area, and the specimens from Zhejiang, which is a low‐incidence area. Furthermore, different mutational spectra were found in the tumor samples from these two geographic areas: In tumor samples from Linxian, the most common substitution mutation was a transversion in exon 5, whereas the most common mutations in tumor samples from Zhejiang were transitions in exon 7. CONCLUSIONS The data suggest that the mutation and overexpression of p53 may play important roles in the development of ESCC. The changes in p53 may reflect environmental exposure to the different combinations of mutagenic factors and genetic instability demonstrated by the populations in Linxian and Zhejiang. The overexpression of p53 protein may have significance as a prognostic factor for patients with esophageal carcinoma. Cancer 2004. © 2004 American Cancer Society.