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目的 探讨E 钙粘素 (E cad)基因及其启动子上CpG位点甲基化与前列腺癌细胞E cad基因失活的关系。方法 通过显微解剖技术收集 35例前列腺癌组织细胞标本 ,并按病理分级分为低级别组 (Ⅰ～Ⅱ ) 15例和高级别组 (Ⅲ～Ⅴ ) 2 0例 ,采用硫酸氢钠基因组测序法检测E cad基因甲基化状态 ,采用免疫组织化学方法检测癌细胞内E cad蛋白表达 ,分析E cad基因甲基化与其表达、肿瘤病理分级间的关系。结果 低级别的前列腺癌和高级别肿瘤E cad基因甲基化阳性率分别为 33 % (5 /15 )和 70 % (14/ 2 0 ) ,低级别标本甲基化主要位于外显子区域 ;而在高级别标本中 ,启动子区域也发生甲基化。免疫组织化学染色 ,在甲基化阳性的细胞 ,阴性染色的癌细胞比例随病理级别的增高而增加。结论 前列腺癌E cad基因高甲基化状态 ,特别是启动子区域甲基化是引起该基因失活并导致前列腺癌浸润进展的因素之一。
Objective To investigate the relationship between methylation of E cad gene and promoter CpG methylation and E cad gene in prostate cancer cells. Methods Tissue samples of 35 cases of prostate cancer were collected by microdissection and divided into 15 cases of low grade group (Ⅰ ~ Ⅱ) and 20 cases of high grade group (Ⅲ ~ Ⅴ) according to pathological grade. The methylation status of E cad gene was detected by immunohistochemistry. The expression of E cad protein in cancer cells was detected by immunohistochemistry. The relationship between methylation of E cad gene and its pathological grade was analyzed. Results The positive rates of E cad gene methylation in low-grade prostate cancer and high-grade tumor were 33% (5/15) and 70% (14/20) respectively. The methylation of low-grade specimen was mainly located in exon region. In high-grade specimens, the promoter region also occurs methylation. Immunohistochemical staining, methylation-positive cells, negative staining of the proportion of cancer cells increased with the pathological grade increased. Conclusion The hypermethylation status of E cad gene in prostate cancer, especially the promoter methylation, is one of the factors that cause the gene inactivation and lead to the progression of prostatic cancer.