Relationship between Methylation Status of p16 Tumor Suppressor Gene and Clinicopathologic Behavior of Stomach Cancer

Park, Chan Won; Lee, Dong Hyun; Kim, Ji Young; Seo, Soo Boon; Ju, Hyung Joon; Kim, Gwang Ha; Heo, Jeong; Kang, Dae Hwan; Cho, Mong; Yang, Ung Suk

Abstract

BACKGROUND/AIMS: Hypermethylation of the p16 tumor suppressor gene is one of the most widely reported epigenetic event to occur in the development of human cancers. The authors investigated the methylation status of p16 gene in stomach cancer (SC) tissues and their adjacent non-tumorous tissues, and analyzed relationship between the methylation status and clinicopathologic patterns of SC.
METHODS
Promoter methylation of p16 gene was evaluated by methylation-specific polymerase chain reaction in 36 SCs and their adjacent non-tumorous tissue samples.
RESULTS
Methylation of p16 gene was detected in 16 (44.4%) SC tissues and 4 (13.8%) adjacent non-tumorous tissues (p=0.008). Of 36 cancer tissues, methylation was detected in 5 of 16 early and in 9 of 20 advanced (p=0.154). The 36 cases could be classified into 23 intestinal and 13 diffuse types according to Lauren's classification. Among them, 13 intestinal and 3 diffuse types were positive for methylation (p=0.052). Methylation frequencies in well, moderately, and poorly differentiated tumors were 25%, 46.2%, and 63.6%, respectively (p=0.359). Nine tumors with lymph node metastasis and 7 tumors without lymph node metastasis showed p16 gene methylation (p=0.112).
CONCLUSIONS
The methylation of p16 gene was observed more frequently in the SC tissues than in adjacent non-tumorous tissues. Our study suggests that the methylation of p16 gene may be related to clinicopathologic parameters such as Lauren's classification, depth of invasion, grade of differentiation, and lymph node metastasis.