淋巴结微转移及相关蛋白检测在大肠癌患者Dukes分期、治疗和预后中的意义  

Lymph node micrometastases and expression of metastasis-related gene proteins in patients with colorectal cancer

作　　者：范跃祖[1] 李新平[1] 刘文方[1] 李光明[1] 

机构地区：[1]上海同济大学附属同济医院普外科,200065

出　　处：《中华外科杂志》2006年第3期181-185,共5页Chinese Journal of Surgery

基　　金：铁道部科研资助项目(J2000Z131);上海市卫生局基金资助项目(034109)

摘　　要：目的探讨淋巴结微转移(LNMM)和nm23H1、基质金属蛋白酶9(MMP9)、金属蛋白酶2组织抑制因子(TIMP2)蛋白检测及其相关性在大肠癌患者Dukes分期、治疗和预后中的意义。方法应用免疫组化SABC法检测30例DukesB期大肠癌淋巴结细胞角蛋白20(CK20)和癌组织nm23H1、MMP9、TIMP2蛋白表达,另对同期30例DukesC和D期大肠癌患者检测nm23H1、MMP9和TIMP2;随访、记录患者的临床病理参数和生存资料,分析其相关性。结果(1)26.7%DukesB期大肠癌患者、7.8%DukesB期大肠癌淋巴结存在CK20阳性。(2)DukesB期大肠癌nm23H1、MMP9表达与DukesC和D期差异显著(P<0.05);nm23H1表达下降和(或)MMP9表达增强与LNMM相关(P<0.05),两者预测大肠癌LNMM敏感性和特异性分别为62.5%和81.8%、75.0%和69.8%,联合检测特异性则达90.9%;而TIMP2与Dukes分期、LNMM无关。(3)DukesB期LNMM(+)患者癌复发转移率明显高于同期LNMM(-)组(P<0.05),而生存率则降低(P<0.05);nm23H1(-)LNMM(+)、MMP9(+)LNMM(+)患者生存期明显短于nm23H1(+)LNMM(-)、MMP9(+)LNMM(-)组(P<0.05)。结论CK20免疫组化可检出大肠癌LNMM;DukesB期大肠癌nm23H1、MMP9表达与LNMM相关,且表达异常LNMM患者预后差;联合检测淋巴结CK20和癌组织nm23H1、MMP9表达,对大肠癌Dukes分期、术后辅助化疗和预后判断有重要意义。Objective To study lymph node micrometastases （LNMM） , expression of nm23-H1, MMP9, TIMP2 proteins, and their relationship and clinical significance in patients with stage Dukes B colorectal cancer. Methods Thirty patients with stage Dukes B colorectal cancer were studied. LNMM in these patients was detected by immunohistochemical anti-cytokeratin 20 （CK20） staining. The expression of nm23-H1, MMP9 and TIMP2 proteins in primary tumors was examined by Strept-avidin-biotin complex method. Clinical-pathological data and survival of each patient were recorded and analyzed. Results （ 1 ） The positive dyeing of CK20 was observed in 26. 7% for cases and in 7.8% for lymph nodes of 30 patients with stage Dukes B colorectal cancer. （2）Different expression of nm23-H1 and MMP9 proteins in the patients between stage Dukes B and stage Dukes CD was observed （ P 〈 0. 05）. The decreased nm23-H1 expression, and/or the increased MMP9 expression in primary stage Dukes B tumors were significantly associated with LNMM （P 〈 0.05）. Sensitivity and specificity for detection of LNMM by using nm23-H1 or MMP9 were respectively 62. 5% and 81.8% or 75.0% and 69. 8%. If by combining nm23-H1 with MMPg, specificity for detection of LNMM became 90.9%. The expression of TIMP2 protein wasn＇t related with stage Dukes and LNMM. （3） The percent of tumor recurrence and/or metastasis for the stage Dukes B patients with LNMM was significantly higher than that for the patients without LNMM （ P 〈0. 05） , but the survival percent for the patients with LNMM was significantly lower than that for the patients without LNMM. The outcome for the patients with nm23-H1 （ - ） LNMM （ ＋ ） or MMP9 （ ＋ ） LNMM （ ＋ ） was significantly worse than that for patients with nm23-H1（＋） LNMM（-） orMMPg（＋） LNMM（-） （P〈0.05）. Conclusions LNMM is detected by immunohistochemical anti-CK20 staining. The expression of nm23-H1 and MMP9 in primary stage Dukes B tumors was significantly associated with L

关 键 词：结肠直肠肿瘤 淋巴转移 角蛋白 核苷二磷酸激酶A 明胶酶B 

分 类 号：R735.34[医药卫生—肿瘤] R735.2[医药卫生—临床医学]