p16 promoter hypermethylation: a useful serum marker for early detection of gastric cancer.
OBJECTIVE
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.


CONCLUSIONS
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.
Abbaszadegan
Mohammad Reza
MR
Division of Human Genetics, Immunology Reserach Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad 9196773117, Iran. abbaszadeganmr@mums.ac.ir
Moaven
Omeed
O
Sima
Hamid Reza
HR
Ghafarzadegan
Kamran
K
A'rabi
Azadeh
A
Forghani
Mohammad Naser
MN
Raziee
Hamid-Reza
HR
Mashhadinejad
Ali
A
Jafarzadeh
Mostafa
M
Esmaili-Shandiz
Ehsan
E
Dadkhah
Ezzat
E
D000368:Aged; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D005260:Female; D016480:Helicobacter pylori / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics*; D013447:Sulfites / Q000737:chemistry
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D013447:Sulfites; C042345:hydrogen sulfite