Methylation of p16INK4A and p57KIP2 are involved in the development and progression of gastric MALT lymphomas

Abstract

p16INK4A and p57KIP2 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 p16INK4A and p57KIP2 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 p16INK4A was detected in 10% of cases, while methylation of p57KIP2 was not detected. In low-grade MALT lymphomas, p16INK4A and p57 KIP2 were methylated in 41.7 and 29.2% of the cases, respectively. In diffuse large B-cell lymphomas, methylation of p16INK4A and p57 KIP2 was found in 72.7 and 36.4% of the cases, respectively. All but one case with p16INK4A and p57KIP2 methylation was H. pylori positive and most of them were stage I. Our results indicate that methylation of p16INK4A followed by p57KIP2 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. © 2006 USCAP, Inc All rights reserved.