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©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 7, 2008; 14(13): 2055-2060
Published online Apr 7, 2008. doi: 10.3748/wjg.14.2055
p16 promoter hypermethylation: A useful serum marker for early detection of gastric cancer
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
Mohammad Reza Abbaszadegan, Omeed Moaven, Azadeh A'rabi, Ezzat Dadkhah, Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad 9196773117, Iran
Hamid Reza Sima, Department of Internal Medicine, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad 9137913316, Iran
Kamran Ghafarzadegan, Department of Pathology, Omid Hospital, Mashhad University of Medical Sciences, Mashhad 9176613775, Iran
Mohammad Naser Forghani, Department of Surgery, Omid Hospital, Mashhad University of Medical Sciences, Mashhad 9176613775, Iran
Hamid Reza Raziee, Department of Oncology, Omid Hospital and Cancer Research Center, Mashhad 9176613775, Iran
Ali Mashhadinejad, Mostafa Jafarzadeh, Ehsan Esmaili-Shandiz, Gastroenterology Research Center, Mashhad University of Medical Sciences, Mashhad 9137913316, Iran
Author contributions: Abbaszadegan MR and Moaven O contributed equally to this work; Abbaszadegan MR, Moaven O, Sima HR, Ghafarzadegan K and Raziee HR designed the research; Abbaszadegan MR, A’rabi A, Moaven O, Ghafarzadegan K, Mashhadinejad A, Forghani MN, Esmaili-Shandiz E, and Dadkhah E performed the research; Moaven O and Jafarzade M analyzed the data; and Abbaszadegan MR, Moaven O and Sima HR wrote the paper.
Correspondence to: Mohammad Reza Abbaszadegan, MT (ASCP), PhD, Associate Professor, Director, Division of Human Genetics, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad 9196773117, Iran. abbaszadeganmr@mums.ac.ir
Telephone: +98-511-7112343
Fax: +98-511-7112343
Received: December 21, 2007
Revised: February 10, 2008
Published online: April 7, 2008
AIM: To determine p16 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 H pylori 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.
