4.1B蛋白在食管鳞状细胞癌中的异常表达及其分子机制

Abnormal expression of 4.1B protein in esophageal squamous cell carcinoma and its molecular mechanism

目的:研究4.1B蛋白在食管鳞状细胞癌组织中的表达及异常表达的分子机制。方法:采用免疫组织化学法检测110例石蜡包埋食管鳞状细胞癌及癌旁组织中4.1B蛋白的表达水平。随机选取其中29例,应用微卫星PCR技术检测4.1B等位基因的杂合子丢失情况。应用甲基化特异PCR技术检测33例新鲜食管鳞状细胞癌手术标本的4.1B基因启动子区域的甲基化状态。结果:食管鳞状细胞癌组织中4.1B蛋白的阳性表达率为60.9%(67/110),癌旁正常组织的阳性表达率为94.5%(104/110),2组之间差异有统计学意义(χ2=35.945,P<0.01)。食管鳞状细胞癌高、中、低分化组的阳性表达率分别为74.4%(29/39)、61.8%(21/34)和45.9%(17/37),3组之间差异有统计学意义(χ2=6.453,P<0.05)。在20.7%(6/29)的食管鳞状细胞癌组织中,分别于D18S481、D18S62和D18S391这3个微卫星位点检测到4.1B等位基因的杂合子缺失。在33例新鲜手术标本中,有69.7%(23/33)的食管鳞状细胞癌组织检测出4.1B基因启动子区域的甲基化。结论:4.1B蛋白在食管鳞癌组织中的阳性表达率明显低于癌旁正常组织,食管鳞状细胞癌的分化程度与其表达量呈正相关;启动子区域的异常甲基化可能是4.1B蛋白阴性表达的重要原因。

Objective：To examine the expression of 4.1B protein in esophageal squamous cell carcinoma （ESCC） and explore the molecular mechanisms for the abnormal expression of 4.1B. Methods： Immunohistochemistry was used to examine 4.1B expression of 110 ESCC specimens. Microsatellite analysis was used to determine whether loss of heterozygosity （LOH） occurred in 29 specimens randomly selected from the 110 cases. Methylation-specific PCR （MSP） was performed to determine the methylation status of promoter regions. Results： The positive rates of 4.1B expression were 60.9% （67/110） and 94.5% （ 104/1 10） in the ESCC tissues and adjacent normal tissues, respectively, with a significant difference （χ^2 = 35. 945, P 〈 0.01 ）. The positive rates of 4.1B in the well, moderately, and poorly differentiated ESCC specimens were 74.4% （29/39） , 61.8% （21/34） , and 45.9% （ 17/37）, respectively. The difference was significant （X2 =6. 453, P 〈0.05）. LOH was detected at D18S481, D18S62, and D18S391 microsatellites in 20.7% （6/29） ESCC specimens. 4. 1B promoter methylation was detected in 69.7% （23/33） fresh ESCC specimens. Conclusions： The positive expression of 4.1B protein was significantly lower in esophageal squamous cell carcinoma than that in normal adjacent tissues. The differentiation degree of ESCC had positive correlation with the expression of 4.1 B. Abnormal methylation in the promoter region might be an important explanation for the negative expression of 4.1 B protein.