Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Anticancer Res. 2010 Jan;30(1):239-44.
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.
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.
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.
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.
探讨抑癌基因 CpG 岛甲基化（CIHM）与胃癌临床病理形态学特征的关系。
采用甲基化特异性聚合酶链反应（MSP）检测 146 例胃癌组织中 p14、p16、凋亡相关蛋白激酶（DAPK）和 E-钙黏蛋白（CDH1）基因的 CIHM 状态。将 3 个或 3 个以上 CpG 岛甲基化定义为 CIHM 高。
p14、p16、CDH1 和 DAPK 基因的 CIHM 分别见于 70 例（47.9%）、26 例（17.8%）、104 例（71.2%）和 127 例（87.0%）。63 例（43.2%）为 CIHM 高。CIHM 状态与不同分期、Lauren 分型、解剖部位、静脉和淋巴管浸润、淋巴结转移、远处转移或腹膜播散无相关性。然而，在早期胃癌病例中，伴有溃疡的凹陷型 DAPK 基因 CIHM 发生率明显较低。Borrmann Ⅳ型晚期胃癌中 CIHM 高的发生率明显较低。Borrmann Ⅳ型病例的平均甲基化数量也较低。
本研究结果提示，DAPK 基因 CIHM 和 CIHM 高与早期胃癌凹陷型伴溃疡和 Borrmann Ⅳ型进展期胃癌的形态学表现相关。
