耐药基因相关蛋白在胃癌术后辅助化疗及预后评价中的意义

Significance of muitidrug resistance gene-associated proteins in the postoperative adjuvant chemotherapy for gastric carcinoma and the prognosis

目的探讨多药耐药基因（MDR）相关产物在胃癌组织中的表达及其对胃癌根治术后辅助化疗及预后评价的意义。方法用免疫组织化学方法检测99例胃癌组织中拓扑异构酶Ⅱ（ToPo Ⅱ）、多药耐药相天蛋白（MRP）和谷胱甘肽-S-转移酶（GST-π）的表达，分析其与胃癌临床病理特征的关系。将ToPo Ⅱ阴性表达、MRP阳性表达和GST-π阳性表达作为3个可能的危险因素，并将本组患者分成高危耐药组（2～3个危险因素）和低危耐药组（0～1个危险因素），比较两组患者术后复发情况、生存率及辅助化疗的有效性.结果ToPo Ⅱ阳性表达率为74．7％．与胃癌组织类型及分化程度有关：MRP阳性表达率为40．4％，与胃癌临床病理因素均无关；GST-π阳性表达率为49．5％．与患者性别和胃癌分化程度有关。3种蛋白各自表达的阳性组与阴性组比较，术后复发率、复发时间及5年生存率的差异均无统计学意义（均P〉0．05）。高危耐药组术后有25例（55．6％）复发．复发时间为（15．2±8．1）个月，与低危耐药组比较，复发率差异无统计学意义（44．4％，P〉0．05），但复发时间早于低危耐药组[（21．3±11．1）个月，P〈0．05]；两组患者术后5年生存率分别为44．4％和55．6％．差异无统计学差异（P〉0．05）．高危耐药组中化疗患者与未化疗患者术后5年生存牢分别为45.8％和42．9％．差异无统计学意义（P〉0．05）；低危耐药组中化疗患者与未化疗患者术后5年生存率分别为70．4％和40．7％．差异有统计学意义（P〈0．05）。结论MDR基因相关产物ToPo Ⅱ、MRP和GST-π的表达与胃癌根治术后辅助化疗的有效性有关．对于高危耐药的患者进行辅助化疗并不能改善预后，

Objective To investigate the expression of multidrug resistance （MDR） geneassociated proteins （MRP） in gastric carcinoma, and their effects on the postoperative adjuvant chemotherapy and the prognosis of patients. Methods The expressions of ToPo Ⅱ ,MRP,GST-π in 99 patients with gastrie carcinoma were detected by immunohistochemistry. The expression and its relationship to the pathological data were analyzed. The positive expression of MRP and GST-π, and the negative expression of ToPo Ⅱ were considered as risk factors. Patients were divided into two groups： a high risk drug-resistant group （2-3 risk factors）and the low risk drug-resistant group （0-1 risk factors）. Postoperative recurrence, survival rate, and efficacy of adjuvant chemotherapy were compared between two groups. Results The positive rate of ToPo Ⅱ was 74.7%, and the expression was associated with types and differentiation of the tumor. The positive rate of GST-π was 49.5% . and the expression was related to the gender and the differentiation. The positive rate of MRP was 40.4% , and there was no relationship between the MRP expression and the pathological finding. There were no significant differenees in the recurrence, time to recurrence, and the 5-year survival rate between the positive and negative group of the three proteins（P〉0.05）. Recurrence was found in 25 cases（55.6%） in the high risk drug-resistant group and the mean time to recurrence was （15.2±8.1） months. The time to recurrence was shorter in the low risk drug- resistant group [ （21.3 ± 11.1 ）months, P〈0.05 ] , but there was no significant difference in the recurrence rate between two groups （P〉0.05）. The 5-year survival rate of the high risk drug-resistant group and the low risk drug-resistant group was 44.4% and 55.6%（P〉0.05）. The 5-year survival rates of patients with or without chemotherapy in the high risk drug-resistant group were 45.8% and 42.9% （P〉0.05）. The 5-year survival rates of patients with or without chemotherapy in the low risk drug-resistant group were 70.4% and 40.7%. The survival rate of patients with chemotherapy was higher than that of the patients without chemotherapy （P〈0.05）. Conclusions The expression of ToPo Ⅱ , MRP and GST-π is associated with the efficacy of postoperative adjuvant chemotherapy. Chemotherapy appears to be more beneficial to patients with low risk drug-resistance.