Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma.
Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma.
复制标题
DOI：
10.1186/1471-2407-10-317
复制
发表时间：
2010-06-22
期刊：
影响因子：
3.8
通讯作者：
Malfertheiner P
中科院分区：
文献类型：
--
作者：
Csepregi A;Ebert MP;Röcken C;Schneider-Stock R;Hoffmann J;Schulz HU;Roessner A;Malfertheiner P
CDKN2A的产物p16是细胞周期的重要调节因子，控制细胞进入s期。在此，我们评估了CDKN2A启动子甲基化和p16蛋白表达在肝细胞癌（HCC）与其他肝脏肿瘤分化中的作用。从85例肝肿瘤患者中获得肿瘤和相应的非肿瘤肝组织样本。利用MethyLight技术和甲基化特异性PCR （methyl- specific PCR， MSP）研究CDKN2A启动子甲基化。在MethyLight分析中，PMR（甲基化参比百分比）≥4%的样品被认为是高甲基化的。利用免疫反应性评分（IRS）从0（无表达）到6（强表达）对81例患者组织切片（n = 148）的p16表达进行免疫组化评估。CDKN2A启动子高甲基化出现在23例hcc（69.7%，平均PMR = 42.34±27.8%）、6例肝转移灶（20.7%，平均PMR = 31.85±18%）和1例癌外组织中。使用MSP， 32%的非肿瘤（n = 85）、70%的hcc、40%的hcc和24%的肝转移灶发生了高甲基化。相应的，p16核表达在5例（10.9%，平均IRS = 0.5） hcc， 23例（92%，平均IRS = 4.9）转移灶中发现，仅偶有在非病变肝组织的肝细胞中发现（平均IRS = 1.2）。cdkn2a -甲基化和p16蛋白表达在hcc与肝转移之间差异有统计学意义（p < 0.01）。CDKN2A基因启动子甲基化和p16表达缺失是HCC患者的特征。
The product of CDKN2A, p16 is an essential regulator of the cell cycle controlling the entry into the S-phase. Herein, we evaluated CDKN2A promoter methylation and p16 protein expression for the differentiation of hepatocellular carcinoma (HCC) from other liver tumors. Tumor and corresponding non-tumor liver tissue samples were obtained from 85 patients with liver tumors. CDKN2A promoter methylation was studied using MethyLight technique and methylation-specific PCR (MSP). In the MethyLight analysis, samples with ≥ 4% of PMR (percentage of methylated reference) were regarded as hypermethylated. p16 expression was evaluated by immunohistochemistry in tissue sections (n = 148) obtained from 81 patients using an immunoreactivity score (IRS) ranging from 0 (no expression) to 6 (strong expression). Hypermethylation of the CDKN2A promoter was found in 23 HCCs (69.7%; mean PMR = 42.34 ± 27.8%), six (20.7%; mean PMR = 31.85 ± 18%) liver metastases and in the extralesional tissue of only one patient. Using MSP, 32% of the non-tumor (n = 85), 70% of the HCCs, 40% of the CCCs and 24% of the liver metastases were hypermethylated. Correspondingly, nuclear p16 expression was found immunohistochemically in five (10.9%, mean IRS = 0.5) HCCs, 23 (92%; mean IRS = 4.9) metastases and only occasionally in hepatocytes of non-lesional liver tissues (mean IRS = 1.2). The difference of CDKN2A-methylation and p16 protein expression between HCCs and liver metastases was statistically significant (p < 0.01, respectively). Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with HCC.
登录
查看更多内容
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
24.5
作者：
Kaneto, H;Sasaki, S;Imai, K
通讯作者：
Imai, K
影响因子：
13.5
作者：
Chaubert, P;Gayer, R;Shaw, P
通讯作者：
Shaw, P
影响因子：
3.3
作者：
Prall, F;Ostwald, C;Nizze, H
通讯作者：
Nizze, H
影响因子：
64.5
作者：
Serrano, M;Lee, HW;DePinho, RA
通讯作者：
DePinho, RA