DNA损伤修复蛋白在胆囊病变组织中的表达及其临床意义

Expression and clinical significances of DNA damage repair proteins in the benign and malignant lesions of gallbladder

目的研究胆囊腺癌、癌旁组织、腺瘤性息肉和慢性胆囊炎组织中DNA损伤修复蛋白hMSH_2和hMLH_1表达及其临床意义。方法选取胆囊腺癌108例、癌旁组织46例、腺瘤性息肉15例和慢性胆囊炎35例手术切除标本常规作石蜡包埋切片,采用EnVisionTM免疫组化法检测hMSH_2和hMLH_1。结果 hMSH_2和hMLH_1表达阳性率,胆囊腺癌分别为50.0%和49.1%、评分分别为2.2±1.9和2.2±1.8,均明显低于癌旁组织(阳性率分别为84.8%和87.0%;评分分别为3.9±1.3和4.2±1.2)、腺瘤性息肉(阳性率分别为80.0%和86.7%;评分分别为3.7±1.3和4.0±1.1)及慢性胆囊炎组织(阳性率分别为88.6%和88.6%;评分分别为4.1±1.1和3.9±1.1)(P<0.05);不同类型良性病变中2种DNA损伤修复蛋白表达阳性率及其评分均无明显差异(P>0.05)。hMSH_2和hMLH_1表达阴性的良性病变胆囊上皮均呈中至重度不典型增生的病理形态学表现。腺瘤癌变或高分化腺癌、肿块最大径<2 cm,无淋巴结转移及未侵犯周围组织的病例hMSH_2和hMLH_1表达阳性率及其评分均明显地高于低分化腺癌、肿块最大径≥2 cm、淋巴结转移及侵犯周围组织病例(P<0.05);2种DNA损伤修复蛋白表达与患者性别、年龄及有无胆囊结石均无明显关系(P>0.05)。结论 DNA损伤修复蛋白表达水平均为反映胆囊腺癌发生、进展、临床生物学行为及预后的重要标记物,检测其表达水平对指导预防和早期发现、临床化疗胆囊癌可能有一定临床意义。

Objective To study the expressive levels of DNA damage repair proteins hMSH2 and hMLH1, and detect their significances in the tissues of adenocarcinoma, pericancer, adenomatous polyp and chronic choleeystitis. Methods Envision TIM immunohistochemical method for determining the levels of （hMSH2 and hMLH1） were used in routinely paraffin - embedded sections from the operated specimens of gallbladder adenecarcinoma （ n = 108）, pericancerous tissues （n = 46）, adenomatous polyp（n = 15）, and chronic cholecystitis （n = 35）. Results The positive rates and scores of hMLH1 and hMSH2 were significantly lower in gallbaldder adenecarcinoma than those in pericancerous tissues, adenomatous polyp, and chronic cholecystitis （ P 〈 0.05 ）. The positive rates and scores of hMLH1 and hMSH2 had no significant difference in different types of benign lesions （ P 〉 0.05 ）. The positive rates and scores of hMLH1 and hMSH2 were significantly higher in the adenomatous caneeration or well differentiated adenecarcinoma, the maxinal diameter of mass 〈 2 cm, no - metastasis of lymphnode, and no - inva- sion of regional tissues than those in the ones of poorly - differentiated adenocarinoma, the maximal diameter, of mass...〉 2 cm, metastasis of lymphnode, and invasion of regional tissues （ P 〈 0.05 ）. But no differences were found among the expressive levels of hMLHl and hMSH2 and the sex, age, with or without gallstone of the patients with gallbladder adenocarcinoma（ P 〉 0.05）. Conclusion The expressive levels of hMLH1 and hMSH2 might be important biological markers for reflicting the carcinogenesis, progression clinical biological behaviors and prognosis of gallbladder adenoearcinoma. And assaying their expressive levels might have importand clinical values for guide chemotherapy of patients with gallbladder adenocarcinoma.