Zhang Fan, Wang Li, Wu Ping Ping, Yan Zhao Wen, Zheng Lin, Yu Ying Yan, Jiang Xu Cheng
Department of Pathology, Shanghai Second Medical University, Shanghai, China.
Chin J Dig Dis. 2004;5(4):149-55. doi: 10.1111/j.1443-9573.2004.00172.x.
Inactivation of the tumor suppressor gene by CpG hypermethylation is a common event in a variety of tumors. The present study was designed to be a comprehensive analysis of p16/INK4 methylation in carcinomas of the upper digestive tract.
Series of esophageal carcinomas (34 cases) and gastric carcinomas (25 cases) were examined for CpG methylation in p16/INK4 using methylation-specific PCR (MSP). The tissue sections underwent MSP in situ and were then examined microscopically. Immunohistochemical detection of the expression of p16 in the tumor specimens was also performed.
Immunohistochemistry detected positive p16 expression in 8 cases of esophageal squamous cell carcinoma and 15 cases of gastric carcinoma. In esophageal carcinoma, hypermethylation of the p16/INK4 promoter region was detected in 5 cases without statistical correlation with its loss of expression, whereas in the gastric carcinomas, p16 expression was positively correlated with the T-classification (r = 0.488, P = 0.01); p16/INK4 methylation was identified in 8 cases. In addition, p16 expression was lower in the methylated samples than in the non-methylated samples (25% vs 76.47%, P = 0.03). Analysis of the MSP-in-situ sections showed that the distribution of methylated cells in esophageal carcinoma differed from that in gastric carcinoma.
The role of DNA methylation in the silence of p16/INK4 may different between these two types of upper digestive tract tumor.
肿瘤抑制基因因CpG高甲基化而失活在多种肿瘤中是常见事件。本研究旨在对上消化道癌中p16/INK4甲基化进行全面分析。
采用甲基化特异性PCR（MSP）检测34例食管癌和25例胃癌系列样本中p16/INK4的CpG甲基化情况。对组织切片进行原位MSP检测，然后进行显微镜检查。还对肿瘤标本中p16的表达进行了免疫组化检测。
免疫组化检测发现8例食管鳞状细胞癌和15例胃癌中有p16阳性表达。在食管癌中，5例检测到p16/INK4启动子区域高甲基化，与其表达缺失无统计学相关性；而在胃癌中，p16表达与T分期呈正相关（r = 0.488，P = 0.01）；8例检测到p16/INK4甲基化。此外，甲基化样本中p16表达低于未甲基化样本（25%对76.47%，P = 0.03）。对原位MSP切片的分析表明，食管癌中甲基化细胞的分布与胃癌不同。
DNA甲基化在这两种上消化道肿瘤中p16/INK4沉默中所起的作用可能不同。
