EPCAM在散发性结直肠癌中不同表达的临床病理学意义及其原理分析

Clinicopathological significance of the different expression of EpCAM in sporadic colorectal cancer

目的 探讨上皮细胞黏附分子(EpCAM)在散发性结直肠癌(CRC)中不同表达与临床病理指标的关系及其原理。方法 收集139例CRC组织蜡块制作组织芯片,使用组织芯片与免疫组化方法,检测EpCAM、β-catenin, c-Myc及Ki-67的表达情况,分析其相关性,并对EpCAM染色结果与CRC临床病理学指标的相关性进行分析。结果 在139例散发性CRC病例中,EpCAM在CRC中呈细胞膜强表达者占85.7%,弱表达或缺失者占14.3%与高表达者相比,弱表达病例的TNM分期(P=0.003)及淋巴结转移率(P<0.001)显著升高,二者在患者性别、年龄、发病部位、肿瘤分化等方面无显著差异。且弱表达者β-catenin的异常表达率、c-Myc的核表达率及Ki-67的增殖指数均高于强表达者。结论 既往研究认为,EpCAM过表达是CRC侵袭转移及不良预后的指标,然而本研究表明,EpCAM在部分散发性CRC的病例中膜表达减弱,这样的病例具有更高的肿瘤分期和淋巴结转移率。其原因可能与调节膜内蛋白水解(RIP)导致EpCAM胞内结构域(EpICD)的蛋白水解裂解进入胞质触发信号级联,导致Wnt/β-catenin通路的激活有关。

Objective To explore the relationship between the different expression of the epithelial cell adhesion molecule(EpCAM) and the clinicopathological indicators in sporadic colorectal cancer(CRC). Methods A total of 139 colorectal cancer tissue wax blocks were collected for tissue microarray and immunohistochemistry method was used to detect the expression of EpCAM,β-catenin, c-Myc and Ki-67, and to analyze the correlation of EpCAM staining results and CRC clinicopathological indicators. Results Among the 139 sporadic CRC cases, 85.7% of EpCAM showed strong membrane expression, and 14.3% had diminished or absent expression. The TNM stage and lymph node metastasis rate in the weak expression group were significantly higher than those in the strong expression group(P<0.05). But no significant difference in the gender, age and tumor differentiation of the patients. Conclusion Previous studies believe that EpCAM overexpression is an indicator of CRC invasion and metastasis and poor prognosis;however, our study shows that EpCAM membrane expression is weakened in part of sporadic CRC cases, such cases have higher tumor stage and lymph node metastasis rate. The machanism may be related to the proteolytic cleavage of EpCAM proteolytic(RIP) intracellular domain(EpICD) into the cytosol-triggered signaling cascade, leading to the activation of the Wnt/catenin pathway.