Methylation of p16(INK4A) and p57(KIP2) are involved in the development and progression of gastric MALT lymphomas.
p16(INK4A) and p57(KIP2) are inhibitors of cyclin-dependent kinases and their inactivation by methylation has been reported as a major tumorigenic mechanism in tumors. To examine whether methylation of p16(INK4A) and p57(KIP2) is involved in the development and progression of gastric MALT lymphomas, 24 gastric low-grade lymphomas of MALT, 11 diffuse large B-cell lymphomas, and 10 each case of gastric lymphoid follicles with and without Helicobacter pylori infection were studied. H. pylori infection was positive in 85.7% of the gastric lymphomas. In the gastric lymphoid follicles positive for H. pylori, methylation of p16(INK4A) was detected in 10% of cases, while methylation of p57(KIP2) was not detected. In low-grade MALT lymphomas, p16(INK4A) and p57(KIP2) were methylated in 41.7 and 29.2% of the cases, respectively. In diffuse large B-cell lymphomas, methylation of p16(INK4A) and p57(KIP2) was found in 72.7 and 36.4% of the cases, respectively. All but one case with p16(INK4A) and p57(KIP2) methylation was H. pylori positive and most of them were stage I. Our results indicate that methylation of p16(INK4A) followed by p57(KIP2) methylation involves during the tumorigenesis of gastric MALT lymphomas associated with H. pylori infection. As methylation of these two genes was more frequent in the higher grade (P<0.05), it may contribute to the malignant progression of gastric MALT lymphomas.
Min
Ki Ouk
KO
Department of Clinical Pathology, The Catholic University of Korea, College of Medicine, Inchon, Korea.
Seo
Eun Joo
EJ
Kwon
Hi Jeong
HJ
Lee
Eui Jin
EJ
Kim
Won Il
WI
Kang
Chang Suk
CS
Kim
Kyoung-Mee
KM
D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D013274:Stomach Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D050761:Cyclin-Dependent Kinase Inhibitor p57