直肠黏液腺癌组织中四种耐药基因蛋白的表达变化及意义

Significance of expression of 4 drug resistant gene proteins p-gp,TS,GST-π and TopoⅡin mucousadenocarcinoma of the rectum

目的观察直肠黏液腺癌(MUC)组织中多药耐药基因p-糖蛋白(p-gp)、胸苷酸合酶(TS)、谷胱甘肽转移酶-π(GST-π)、DNA拓扑异构酶(TopoⅡ)的表达变化,并探讨其意义。方法应用免疫组化SP法对37例直肠黏液腺癌及261例直肠非黏液腺癌(non-MUC)组织中p-gp、TS、GST-π、TopoⅡ蛋白进行检测,并分析其与MUC临床病理参数的关系。结果直肠黏液腺癌与非黏液腺癌组织中p-gp阳性表达率分别为81.1%、94.5%,TS阳性表达率分别为83.8%、72.0%,GST-π阳性表达率分别为51.4%、73.9%,TopoⅡ阳性表达率分别为62.2%、71.6%,直肠黏液腺癌与非黏液腺癌组织中p-gp、GST-π阳性表达率比较,P均<0.01。GST-π与直肠黏液腺癌分化程度有关,高中分化者GST-π阳性表达率明显高于低分化者(P<0.01),p-gp、TS、TopoⅡ表达与直肠黏液腺癌临床病理参数间无相关性。p-gp与TS表达呈正相关(r=0.349,P<0.05)。结论直肠黏液腺癌组织中TS表达升高,p-gp、GST-π、TopoⅡ表达降低,GST-π表达与直肠黏液腺癌分化程度有关;四种耐药基因蛋白联合检测可为直肠黏液腺癌化疗药物的筛选及个体化治疗方案制定提供依据。

Objective To observe the change of expression of p-gp, TS, GST-n and Topo Ⅱ in mucousadenocarci- noma（MUC） of the rectum, and investigate its significance. Methods The expression of p-gp, TS, GST-π and Topo Ⅱin 37 cases of MUC and 261 cases of non- mucousadenocarcinoma （non-MUC） of the rectum was detected by using immu- nohistochemical SP method. Results The positive expression rate of p-gp in MUC and non-MUC was 81.1% and 94.5%, respectively. The positive rate of TS was 83.8% and 72.0% , the positive rate of GST-π was 51.4% and 73.9%, and the positive rate of Topo Ⅱ was 62.2% and 71.6%. The positive expression rate of p-gp and GST-π in MUC was significantly lower than that in non-MUC （ P 〈 0.01 ）. The expression of GST-π was correlated with tumor degree of differentiation, and the positive rate of GST-π in well or moderately differentiated MUC was significantly higher than that in poorly differentiated MUC （P 〈0.01）. The expression of p-gp, TS and Topo Ⅱ was not correlated with clinical and pathological features of MUC. P-gp expression was positively correlated to TS expression （ P 〈 0.05 ）. Conclusion The expression of TS is heightened and the expression of p-gp, GST-π and Topo Ⅱ is degraded in MUC of the rectum. The expression of GST-π is correlated with tumor degree of differentiation. The joint detection of p-gp, TS, GST-π and Topo Ⅱ will be useful for choo- sing sensitive chemotherapeutic drugs and selecting individual therapeutic regimen in rectum MUC treatment.