Department of Surgery, Saga University Faculty of Medicine, Saga, Japan.
Ann Surg Oncol. 2011 Oct;18(10):3013-9. doi: 10.1245/s10434-011-1636-0. Epub 2011 Mar 16.
To assess whether gene methylation in peritoneal fluid (PF) is clinically feasible for determining micrometastasis to the peritoneum in gastric cancer.
The gene methylation of BNIP3, CHFR, CYP1B1, MINT25, SFRP2, and RASSF2 were analyzed in 107 specimens of PF by quantitative methylation-specific polymerase chain reaction. All patients were placed into one of 3 groups: group A (n = 42), patients with depth of cancer invasion at muscularis propria (MP) or less than MP; group B (n = 45), depth of cancer invasion beyond the MP; and group C (n = 20), histologically diagnosed peritoneal metastasis or cancer cells cytologically defined in the peritoneal cavity. Patients in both groups A and B were diagnosed as having no cancer cells by peritoneal cytology and histology.
The methylation status of the 6 genes was found to be significantly different among the 3 groups (group A, 0-5%; group B, 0-15%; group C, 15-45%; P < 0.01). Furthermore, the rate of positive methylation in any of the 6 genes was significantly different in each group (group A, 7%; group B, 20%; group C, 75%; P < 0.001). Three of 9 patients in group B with positive methylation in any of 6 genes experienced peritoneal recurrence. On the other hand, only 1 of 36 patients without gene methylation experienced peritoneal recurrence (P < 0.05).
DNA methylation in PFs is a possible marker detecting occult neoplastic cells on the peritoneum. Methylation analysis along with a cytological examination might therefore improve the positive detection of cancer cells in PF of gastric cancer.
评估腹腔液（PF）中的基因甲基化是否可用于临床确定胃癌腹膜微转移。
通过定量甲基化特异性聚合酶链反应分析 107 份 PF 标本中的 BNIP3、CHFR、CYP1B1、MINT25、SFRP2 和 RASSF2 的基因甲基化。所有患者分为 3 组：A 组（n=42），癌症浸润深度局限于黏膜肌层或以下；B 组（n=45），癌症浸润深度超过黏膜肌层；C 组（n=20），组织学诊断为腹膜转移或腹腔细胞学检查可见癌细胞。A 组和 B 组的所有患者均通过腹腔细胞学和组织学检查诊断为无癌细胞。
3 组间 6 个基因的甲基化状态存在显著差异（A 组，0-5%；B 组，0-15%；C 组，15-45%；P<0.01）。此外，每组中任何 6 个基因的阳性甲基化率均存在显著差异（A 组，7%；B 组，20%；C 组，75%；P<0.001）。B 组中 9 例有任何 6 个基因阳性甲基化的患者中有 3 例发生腹膜复发。另一方面，36 例无基因甲基化的患者中仅有 1 例发生腹膜复发（P<0.05）。
PF 中的 DNA 甲基化是一种检测腹膜隐匿性肿瘤细胞的可能标志物。因此，与细胞学检查相结合的甲基化分析可能会提高对胃癌 PF 中癌细胞的阳性检出率。
