CpG island promoter methylation (CIHM) status of tumor suppressor genes correlates with morphological appearances of gastric cancer.
CpG island hypermethylation (CIHM) of tumor suppressor genes is one of the major events in the gastric carcinogenesis. We aimed to investigate the association between CIHM status of tumor suppressor genes and clinicopathological and morphological characteristics of gastric cancer.


METHODS
CIHM of p14, p16, Death-associated protein kinase (DAPK) and E-cadherin (CDH1) genes were determined by methylation-specific-polymerase chain Reaction in 146 gastric cancer tissues. CIHM-high was defined as three or more methylated CpG islands.


RESULTS
CIHM pf p14 was found in 70 (47.9%) cases, in 26 (17.8%) for p16, in 104 (71.2%) for CDH1 and in 127 (87.0%) for DAPK. CIHM-high was also found in 63 cases (43.2%). No association was found between between CIHM status and different staging, Lauren's subtypes, anatomic location, venous and lymphatic invasion, lymph node metastasis, distant metastasis, or peritoneal dissemination. However, among early gastric cancer cases, the depressed type with ulceration presented a significantly lower prevalence of CIHM of DAPK. In addition, Borrmann type IV cases presented significantly lower prevalence of CIHM-high among advanced gastric cancer. The Borrmann type IV cases also presented lower mean methylation number.


CONCLUSIONS
The present results suggest that CIHM of DAPK and CIHM-high were associated with the morphological appearance of depressed type with ulceration in early gastric cancer, and Borrmann type IV advanced gastric cancer, respectively.
Tahara
Tomomitsu
T
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan. tomomiccyu@yahoo.co.jp
Shibata
Tomoyuki
T
Arisawa
Tomiyasu
T
Nakamura
Masakatsu
M
Yamashita
Hiromi
H
Yoshioka
Daisuke
D
Okubo
Masaaki
M
Yonemura
Joh
J
Maeda
Yoshiteru
Y
Maruyama
Naoko
N
Kamano
Toshiaki
T
Kamiya
Yoshio
Y
Fujita
Hiroshi
H
Nakagawa
Yoshihito
Y
Nagasaka
Mitsuo
M
Iwata
Masami
M
Hirata
Ichiro
I
D000368:Aged; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C513384:CDH1 protein, human; C000614131:CDKN2A protein, human; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D025803:Tumor Suppressor Protein p14ARF; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases