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p16 promoter hypermethylation:A useful serum marker for early detection of gastric cancer

World Journal of Gastroenterology 2008年第13期14卷 2055-2060页

作者： Mohammad Reza Abbaszadegan Omeed Moaven Hamid Reza Sima Kamran Ghafarzadegan Azadeh A'rabi Mohammad Naser Forghani Hamid Reza Raziee ali mashhadinejad Mostafa Jafarzadeh Ehsan Esmaili-Shandiz Ezzat Dadkhah Division of Human Genetics Immunology Research Center Avicenna Research Institute Mashhad University of Medical Sciences Mashhad *** Iran Department of Internal Medicine Imam Reza Hospital Mashhad University of Medical Sciences Mashhad *** Iran Department of Pathology Omid Hospital Mashhad University of Medical Sciences Mashhad *** Iran Department of Surgery Omid Hospital Mashhad University of Medical Sciences Mashhad *** Iran Department of Oncology Omid Hospital and Cancer Research Center Mashhad *** Iran Gastroenterology Research Center Mashhad University of Medical Sciences Mashhad *** Iran

AIM： TO determine p15 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS： Samples were obtained from 52 histologically confirmed cases of gastric adenocarcinoma. Gastric tissue and serum of 50 age- and sex-matched individuals with normal gastroscopy and biopsy were obtained as control samples. Methylation-specific polymerase chain reaction （MSP） was used to evaluate methylation status of p16 promoter, p16-protein expression was analyzed by immunohistochemical staining on paraffin-embedded sections. RESULTS： Methylation was detected in 44.2% （23/52） of tumoral tissues. 60.9% of them were also methylated in serum, i.e., 26.9% of all patients （14/52）. Methylation was not detected in tissue and sera of control samples. p16-protein expression was decreased in 61.5% of cases （32/52）, and was significantly associated with promoter hypermethylation （P 〈 0.001）. Methylation was significantly more frequent in higher pathological grades （P 〈 0.05）. Methylation was not associated with other clinicopathological features and environmental factors including Hpylori infection and smoking. CONCLUSION： p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.

关键词： Gastric cancer p16 Hypermethylation Methylation specific PCR

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