Department of Gastro-intestinal Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
Oncol Rep. 2012 Mar;27(3):637-42. doi: 10.3892/or.2011.1547. Epub 2011 Nov 10.
Post-translational histone modifications are known to be altered in cancer tissues, and differences in the histone modification levels have recently been used to predict the clinical outcome in patients with certain types of cancer. In this study, we evaluated the immunohistochemical staining patterns of histone H3 dimethylation and acetylation in metachronous liver metastasis of colorectal carcinomas and examined its correlation with patient prognosis. Double 2 mm core tissue microarrays were made from 54 paraffin-embedded samples of liver metastasis from colorectal adenocarcinoma, and were examined by an immunohistochemical analysis of histone H3 lysine 4 (H3K4) dimethylation, histone, H3 lysine 9 (H3K9) dimethylation and histone H3 lysine 9 (H3K9) acetylation. Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were then examined for correlations with the clinicopathological parameters and clinical outcome. Dimethylation of H3K4 correlated with the tumor histological type (P=0.043), and acetylation of H3K9 correlated with the tumor histological type (P=0.016). In addition, lower levels of H3K4 dimethylation correlated with a poor survival rate (P=0.035). The multivariate survival analysis showed that the H3K4 dimethylation status is an independent prognostic factor for colorectal cancer patients (P=0.011). We suggest that the pattern of histone modification as detected by immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.
组蛋白翻译后修饰已知在癌症组织中发生改变，并且组蛋白修饰水平的差异最近已被用于预测某些类型癌症患者的临床结局。在这项研究中，我们评估了结直肠癌肝转移的组蛋白 H3 二甲基化和乙酰化的免疫组织化学染色模式，并检查了其与患者预后的相关性。从 54 例结直肠腺癌肝转移的石蜡包埋样本中制作了 2 个 2mm 核心组织微阵列，并通过组蛋白 H3 赖氨酸 4（H3K4）二甲基化、组蛋白 H3 赖氨酸 9（H3K9）二甲基化和组蛋白 H3 赖氨酸 9（H3K9）乙酰化的免疫组织化学分析来检查。将每种组蛋白修饰的阳性肿瘤细胞染色用于将患者分类为低染色组和高染色组，然后检查与临床病理参数和临床结局的相关性。H3K4 的二甲基化与肿瘤组织学类型相关（P=0.043），而 H3K9 的乙酰化与肿瘤组织学类型相关（P=0.016）。此外，H3K4 二甲基化水平较低与生存率降低相关（P=0.035）。多变量生存分析显示，H3K4 二甲基化状态是结直肠癌患者的独立预后因素（P=0.011）。我们建议，通过免疫组织化学检测到的组蛋白修饰模式可能是结直肠癌肝转移的独立预后因素。
