结直肠癌组织中TP/DPD表达的研究  

Expression of TP,DPD is related with fluoropyrimidines sensitivity in colorectal cancer

作　　者：赵任[1] 郁宝铭[1] 于颖彦[1] 马韬[1] 朱正纲[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院普外科,上海消化外科研究所上海200025

出　　处：《中国癌症杂志》2006年第3期186-188,192,共4页China Oncology

摘　　要：背景与目的:胃肠道肿瘤患者对氟尿嘧啶类药物的反应率存在很大个体差异,原因在于肿瘤内氟尿嘧啶类药物代谢酶[1,2],胸苷磷酸化酶(TP)和二氢嘧啶脱氢酶(DPD)水平的差异;本文探讨TP和DPD在大肠癌的表达和定位。方法:21对正常大肠粘膜及大肠癌手术切除标本,采用ELISA、免疫组织化学检测与临床病理指标相结合。结果:21对结直肠癌标本中,肿瘤组织与正常大肠粘膜的平均TP含量分别为(60.25±36.18)U/mg和(22.37±13.69)U/mg(P<0.01)。肿瘤与正常大肠粘膜内平均DPD分别为(12.75±5.86)U/mg和(14.02±7.48)U/mg。免疫组织化学染色显示,TP与DPD既可出现在肿瘤细胞内,也广泛存在于癌周免疫反应及炎细胞内。TP、DPD表达与Dukes分期等临床病理指标无明显关系。结论:正常大肠粘膜及癌组织中TP与DPD含量的个体间差异是临床氟尿嘧啶类药物有效性及毒副反应差别的理论依据。检测TP表达可用于5-FU前体药物敏感性的预测,检测DPD表达可作为氟尿嘧啶类药物敏感性预测指标。Background and Purpose： The response rate of gastrointestinal carcinoma to 5-FU as a single agent, is only 10% -30%, and differs greatly among patients. Thymidine phosphorylase （TP）/dihydropyrimidine dehydrogenase （DPD） activity could be used as a predictive marker of 5-FU response. The purpose of this study was to investigate TP/DPD expression. Methods： 50% inhibitory concentrations of growth（ IC 30） representing sensitivity to drugs was determined by MTT assay. Immunohistochemical stain was used for TP or DPD localizing study in tumor tissues. Results： In 21 pairs of clinical samples, the average TP level in tumor tissue and normal mucosa was 60.25±36.18 and 22.37±13.69 U/mg respectively; The average DPD level in tumor and normal mucosa was 12.75±5.86 and 14.02±7.48 U/mg respectively. TP or DPD was expressed in some tumor tissues but was also extensively positive in surrounding inflammation cells immmunohistochemically. ConcIusions： TP and DPD are potential indicators in predicting chemosensitivity to fluoropyrimidines. Immunohistochemical method is practical since it can clearly localize the TP or DPD in tumor cells or stromal cells.

关 键 词：胸苷磷酸化酶(TP) 二氢嘧啶脱氢酶(DPD) 氟尿嘧啶类药物 结直肠癌 ELISA 免疫组织化学 

分 类 号：R735.37[医药卫生—肿瘤] R73-36[医药卫生—临床医学]