Methylotion Analysis of p16/INK4A in Gastric Low-Grade Mucosa-Associated Lymphoid Tissue Lymphomas after Helicobacter pylori Eradication Therapy

ABSTRACT

BACKGROUND: Inactivation of p16 has been associated with promoter region hypermethylation in different types of malignancies, including non-Hodgkin's lymphomas (NHLs). This loss of p16 was found frequently in cases of mucosa-associated lymphoid tissue (MALT) lymphomas. Recent studies indicate that promoter hypermethylation is often an early event in tumor progression in the follow-up of NHLs. METHODS: To investigate the usefulness of p16 methylation in the diagnosis and follow-up of gastric low-grade MALT lymphomas, we analyzed methylation status of p16 using methylation-specific polymerase chain reaction methods in the sequential biopsy specimens of 13 patients with gastric low-grade MALT lymphomas undergoing Helicobacter pylori eradication therapy. RESULTS: Five of thriteen cases showed p16 hypermethylation upon diagnosis. In four of five methylation positive cases, abnormal methylation was detected in the specimen even after the treatment, although there were no histologic evidence of disease. This methylation disappeared in the later samples of two of the cases, and they have remained in complete remission. Immunohistochemically, the loss of p16 protein expression was detected in one of three methylation-positive cases, and in none of the methylation-negative cases. CONCLUSIONS: These results suggest that p16 methylation is relatively fequent in low-grade gastric MALT lymphomas, and it may have clinical applications in the management and follow-up of low-grade gastric MALT lymphomas.