β-catenin与大肠癌干细胞标记物EpCAM^(high)/CD44^+在大肠癌中的表达及临床意义

Expression of β-catenin and colorectal cancer stem cells marker EpCAM^(high)/CD44^+ in colorectal cancer and their clinical significance

目的探讨Wnt/β-catenin通路对大肠癌干细胞的调节及侵袭转移能力的影响。方法免疫组化双重染色法检测80例大肠癌患者原发灶及10例肝转移灶组织中大肠癌干细胞标记物EpCAMhigh/CD44+的表达,免疫组化SP法检测上述组织中Wnt通路关键蛋白β-catenin的表达,分析β-catenin、EpCAM/CD44蛋白在大肠癌组织中的表达与临床病理特征之间的关系及两者的相关性。结果β-catenin在大肠癌及癌旁正常肠黏膜组织的异常表达率分别为55.0%(44/80)和10.0%(2/20),差异有统计学意义(P<0.05)。β-catenin在肝转移灶中的异常表达率为90.0%(9/10)。EpCAM/CD44在大肠癌及癌旁正常肠黏膜组织中的阳性表达率分别为66.3%(53/80)和0(0/20)。大肠癌原发灶中β-catenin的异常表达与性别、年龄、肿瘤大小无关,而与分化程度、浸润深度、Dukes分期及转移密切相关(P<0.05);EpCAMhigh/CD44+表达与性别、肿瘤大小无关,而与年龄、分化程度、浸润深度、Dukes分期及转移密切相关(P<0.05)。EpCAM/CD44在β-catenin异常表达组中的阳性表达率为84.1%,显著高于在其正常表达组的44.4%,差异有统计学意义(P<0.05)。经Pearson相关性分析,β-catenin与EpCAM/CD44的表达呈正相关,差异有统计学意义(r=0.417,P=0.000)。结论 Wnt/β-catenin通路的异常激活有可能参与大肠癌干细胞的异常增殖,进而导致肿瘤的复发转移。

Objective To explore the role of Wnt/f3-catenin signalling pathway in the maintenance, invasion and metastasis of colorectal cancer stem cells. Methods Double immunohistochemical staining was used to detect the expression of EpCAMhigh/ CD44 ~ which was regarded as the marker of eolorectal cancer stem cells in 80 cases of colorectal cancer and 10 corresponding liver me- tastases. The SP method of immunohistochemistry was used to detect the expression of the key protein β-catenin in the Wnt pathway in these tissues mentioned before. The expression and correlation of β-catenin and EpCAM/CD44 in colorectal cancer were analyzed and their roles in the biological behavior of colorectal cancer were analyzed. Results The abnormal expression of β-catenin in colorectal cancer was 55.0% （44/80） , significantly higher than 10% （2/20）in the paraneoplastic normal intestinal mueosa（ P 〈 0. 05 ）. The posi- tive expression of EpCAM/CD44 in colorectal cancer was 66. 3% （53/80） , which was higher than 0 in the paraneoplastic normal intes- tinal mucosa. In the 80 cases of colorectal cancer, the abnormal expression of β-catenin has no correlation with gender, age and the magnitude of the tumor（ P 〉 0. 05 ） , but it was significantly correlated with degree of differentiation, depth of invasion, clinical stage and metastasis （P 〈 0. 05）. In the colorectal cancer, the expression of EpCAMhigh/CD44 ＋ cells had no correlation with gender and the magnitude of the tumor（P 〉 0. 05 ）, but it was significantly correlated with age, degree of differentiation, depth of invasion, clinical stage and metastasis（P 〈 0. 05）. In the corresponding liver metastases, EpCAMhish/CD44 ＋ cells were detected too. In cases with ab- normal expression of β-catenin, the positive expression rate of EpCAM/CIM4 was significantly higher than those with normal expression of β-catenin（84. 1% vs. 44.4% ） , and the difference was statistically significant（P 〈0. 05）. Positive correlation could be found be-tween the expressions of β-catenin and EpCAMhish/cIM4 ＋ （ r = 0. 417, P = 0. 000）. Conclusion The abnormal activation of Wnt/β- catenin signalling pathway may prompt the abnormal proliferation of the colorectal cancer stem ceils, which leads to the recurrence and metastasis of the cancer.