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《Journal of First Military Medical University》 2003-04
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Microsatellite instability and loss of heterozygosity of fragile histidine triad gene in lung hyperplastic lesions

ZHANG Jun-xin, SHEN Hong Department of Pathology, First Military Medical University, Guangzhou 510515, China  
Objective To ascertain weather there is any difference in the hyperplastic lesions in the bronchial endothelia between patients with lung cancer and those with pneumonia, so as to find reliable molecular marker for early diagnosis of "genuine" preneoplastic lesions. Methods With PCR-denaturing polyacrylamide gel electrophoresis and silver-staining, 82 specimens of bronchial hyperplastic lesions obtained from patients with squamous cell carcinoma (SCC) and 57 matched epithelial lesion specimens obtained from patients with pneumonia were examined for loss of heterozygosity (LOH) and microsatellite instability (MI) of fragile histidine triad (FHIT) gene. Results Allelic losses of FHIT were common in hyperplastic lesions from patients with SCC, and the frequencies of LOH and MI of the 4 microsatellite sites, D3S1234, D3S1300, D3S1481, and D3S1313 were significant higher in hyperplastic lesions from SCC patients than in those from pneumonia patients (P0.01). The frequencies of LOH and MI of FHIT gene in cancerous and noncancerous squamous metaplasia were 54%(7/13) and 12%(2/16) respectively, and were 70%(7/10) and 18%(2/8) respectively in cancerous and noncancerous mild to moderate dysplastic lesions. No significant difference was observed between the frequencies of D3S1234, D3S1300, D3S1481, and D3S1313 in cancerous hyperplastic lesions, which were 41%(34/82), 37%(30/82), 38%(31/82), 34(28/82), respectively (P0.05). Conclusion Hyperplastic lesions showed higher frequency of LOH at the 4 microsatellite sites than MI (P0.01). The fact that LOH of FHIT is prevalent in hyperplastic lesions in SCC patients but rare in pneumonic patients indicates the significant difference between cancerous and noncancerous hyperplastic lesions. LOH of FHIT may be an early event in the development of squamous cell carcinoma in the lungs and is crucial in the early stage of carcinogenesis, validating the use of FHIT as a molecular marker to identify "genuine" preneoplastic lesions.
【Fund】: 广东省卫生厅“五个一”科教兴医工程重点项目(粤卫[1996]186)~~
【CateGory Index】: R734.2
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【Secondary References】
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1 SHEN Di;QI Jun;Cancer Institute & Hospital,Peking Union Medical College and Chinese Academy of Medical Sciences;;Research Development of Blood Tumor Marker in Early Diagnosis of Lung Cancer[J];标记免疫分析与临床;2013-05
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