CpG island promoter methylation (CIHM) status of tumor suppressor genes correlates with morphological appearances of gastric cancer.

ABSTRACT

UNLABELLED 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. PATIENTS AND 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. CONCLUSION: 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.