散发性胆囊肿瘤错配修复基因hMLH1、hMSH2和nm23H1基因蛋白表达的研究

Study on Expression of hMLH1、hMSH2 and nm23H1 Gene in Sporadic Gallbladder Tumor

目的探讨hMLH1和hMSH22种错配修复基因和抑癌基因nm23H1蛋白在胆囊肿瘤组织中的表达,评估其在胆囊肿瘤发生、发展和预后判断中的临床意义,为揭示肿瘤发生的病理机制提供实验依据。方法采用Envision免疫组织化学方法,检测70例胆囊肿瘤组织和10例胆囊炎症组织hMLH1、hMSH2和nm23H1蛋白表达变化。结果①在胆囊癌、胆囊良性肿瘤和炎症组织中,hMLH1、hMSH2和nm23H1蛋白表达阳性率差异显著(P<0.05);②在胆囊癌组织中,hMLH1、hMSH2蛋白表达阳性率分别为51.06%、42.55%;有淋巴结转移者hMLH1蛋白表达阳性率(25.00%)和NevinⅣ+Ⅴ期表达阳性率(29.17%)分别低于无淋巴结转移者(70.37%)和NevinⅠ+Ⅱ+Ⅲ期(73.91%),P<0.01,伴肝脏浸润者(27.78%)低于无肝脏浸润者(65.51%),P<0.05;但hMSH2蛋白表达阳性率无显著性差异;③在胆囊癌组织中,nm23H1蛋白表达阳性率为46.81%,有淋巴结转移者(25.00%)低于无淋巴结转移者(62.96%),P<0.01;NevinⅣ+Ⅴ期(29.17%)低于Ⅰ+Ⅱ+Ⅲ期(65.22%),P<0.05;④在胆囊癌组织中,hMSH2蛋白表达阳性者中nm23H1蛋白表达阳性率(65.00%)显著高于hMSH2蛋白表达阴性者(33.33%),P<0.05。结论实验结果提示,DNA错配修复基因hMLH1、hMSH2和nm23H1基因相互协同,参与了胆囊肿瘤发生、发展和转移的过程,可能是胆囊肿瘤发生的1个重要分子机制。

Objective To examine the protein expression of hMLH1/hMSH2 and nm23H1 gene and evaluate their clinical significances in gallbladder tumors, which may provide experimental basis for the mechanism of tumor occurrence and metastasis. Methods Envision immunohistochemistry techniques were used to assess the expression of gene hMLH1、hMSH2 and nm23H1 in 70 cases gallbladder carcinoma and 10 cases chronic cholecystitis tissue. Results ① the frequency of the hMLH1、hMSH2 and nm23H1 expression were significantly different （P 〈 0.05） in gallbladder carcinoma, gallbladder adenoma and chronic cholecystitis tissue. ② The expression of hMLH1、hMSH2 in gallbladder carcinomas was 51.06 %、42.55 %; the positive frequency of hMLH1 in lymph node metastasis（25.00%） and in Nevin Ⅳ ＋ Ⅴ （29.17%） were significantly lower than those without metastasis （70.37%） and Nevin Ⅰ ＋ Ⅱ ＋ Ⅲ （73.91%）, P 〈 0.01; Moreover, it with liver metastasis （27.78%） was lower than those without liver metastasis （65.51%）, P 〈 0.05. However, the positive frequency of hMSH2 was showed no significantly difference. ③ The expression of nm23H1 was 46.81% in gallbladder carcinomas. The cases with lymph node metastasis （25.00%） showed significantly lower than those without lymph node metastasis （62.96 %）, P 〈 0.01, Nevin Ⅳ ＋ Ⅴ （29.17 %） also exhibited lower levels compared with Ⅰ ＋ Ⅱ ＋ Ⅲ （65.22%）, P 〈 0.05; ④ The positive frequency of nm23H1 protein was higher in hMSH2 positive cases than hMSH2 negative cases （P 〈 0.05）. Conclusion The results indicated that the hMLH1、hMSH2 and nm23H1 gene may be take part in the development of gallbladder tumor through effection each other, which were an important molecule mechanism of gallbladder tumors.