T1和T2期结直肠癌淋巴结转移与相关分子标记物表达的关系  

Expression of molecular markers detected by immunohistochemistry and risk of lymph nodemetastasis in stage T1 and T2 colorecrectal cancers

作　　者：王福龙[1] 万德森[1] 卢震海[1] 方淯靖[1] 李力人[1] 陈功[1] 伍小军[1] 丁培荣[1] 孔令亨[1] 林俊忠[1] 潘志忠[1] 

机构地区：[1]华南肿瘤学国家重点实验室中山大学肿瘤防治中心结直肠科,广州510060

出　　处：《中华肿瘤杂志》2013年第4期277-281,共5页Chinese Journal of Oncology

摘　　要：目的探讨影响T1～1、2期结直肠癌淋巴结转移与相关分子标记物表达的关系。方法采用组织芯片和免疫组化技术检测行根治性切除的T1～T2期结直肠癌组织的血管内皮生长因子受体3（VEGFR-3）、表皮生长因子受体（EGFR）、人类表皮生长因子2（HER-2）、胰岛素样生长因子受体1（IGF-1R）、胰岛素样生长因子2（IGF-2）、胰岛素样生长因子结合蛋白1（IGFBP-1）、E-钙黏蛋白（ECAD）、基质金属蛋白酶9（MMP-9）、金属蛋白酶组织抑制剂1（TIMP-1）、Raf激酶抑制蛋白（RKIP）、趋化因子受体4（CXCR4）、微卫星不稳定（MSI）、CD44v6和CDl33的表达情况，采用Logistic回归分析相关分子标记物与淋巴结转移的关系。结果结直肠癌组织中VEGFR-3、EGFR、HER-2、IGF-1R、IGF-2、IGFBP-1、ECAD、CD44v6、MMP-9、TIMP-1、RKIP、CXCR4和CDl33蛋白的表达率分别为44．3％、30．5％、28．1％、63．5％、44．8％、70．9％、45．8％、51．2％、44．3％、41．4％、45．3％、40．9％和49．8％，MSI阳性率为22．2％。Logistic回归分析结果显示，VEGFR-3、HER-2和TIMP-1的表达与淋巴结转移有关。结论VEGFR-3、HER-2和TIMP-1是影响¨～T2期结直肠癌淋巴结转移的独立因素。Objective To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques. Methods Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry： VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis. Results The positive expression rates of biomarkers were as following： VEGFR-3 （44.3%） ,EGFR （30.5%）, HER-2 （28.1%）, IGF-1R （63.5%）, IGF-2 （44. 8%）, IGFBP-1 （70.9%）, ECAD （45. 8%）, CIM4v6 （51. 2%）, MMP-9 （44.3%）, TIMP-1 （41.4%）, RKIP （45.3%）, CXCR4 （40.9%）, and CD133 （49.8%）. The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis. Conclusions VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.

关 键 词：结直肠肿瘤 肿瘤转移 免疫组织化学 寡核苷酸序列分析 生物学标记 

分 类 号：R735[医药卫生—肿瘤]