Dept. of Pathology, Azienda Ospedaliera di Melegnano, Milan, Italy.
Cancer Treat Rev. 2012 Feb;38(1):68-75. doi: 10.1016/j.ctrv.2011.04.002. Epub 2011 May 14.
Epithelial cell adhesion molecule (EpCAM, CD326) is a pleiotropic molecule that potentially offers therapeutic applications in cancer treatment. Initially described as a dominant surface antigen on human colon carcinoma, it is a transmembrane glycoprotein mediating epithelial-specific intercellular cell-adhesion. Recent data suggest that EpCAM is also involved in cell signaling, migration, proliferation and differentiation. Since EpCAM is expressed exclusively in epithelia and epithelial-derived neoplasms, EpCAM can be used as diagnostic marker. Testing for EpCAM is based on morphology and phenotypical staining and can be performed with primary carcinoma tissue and cells harvested from malignant effusions. Stable or highly expressed EpCAM has been detected in most adenocarcinomas and has also been found in metastases, malignant effusions, and cancer stem cells. EpCAM may thus be an ideal tumor antigen candidate to detect circulating and metastasizing cancer cells by microchip technologies. In certain tumor types overexpression was linked to advanced stage of disease and worse overall survival, suggesting EpCAM as a potential prognostic marker. In addition to its diagnostic and prognostic role, EpCAM's broad expression and apparent involvement in tumorigenesis and metastasis point to its potential as a target for immunotherapeutic strategies. The first EpCAM targeting, trifunctional antibody catumaxomab (Removab®) has shown clear clinical benefits in treatment of malignant ascites associated with EpCAM positive carcinomas. Further research and clinical studies should unravel EpCAM's complex role in oncological processes, and expand potential therapeutic applications of EpCAM targeted strategies.
上皮细胞黏附分子(EpCAM,CD326)是一种多功能分子,具有治疗癌症的应用潜力。最初被描述为人类结肠癌的主要表面抗原,它是一种介导上皮细胞特异性细胞间黏附的跨膜糖蛋白。最近的数据表明,EpCAM 还参与细胞信号转导、迁移、增殖和分化。由于 EpCAM 仅在上皮细胞和上皮源性肿瘤中表达,因此可作为诊断标志物。EpCAM 的检测基于形态学和表型染色,可用于原发性癌组织和从恶性积液中采集的细胞。大多数腺癌中都检测到稳定或高度表达的 EpCAM,并且在转移、恶性积液和癌症干细胞中也发现了 EpCAM。因此,EpCAM 可能是一种理想的肿瘤抗原候选物,可通过微芯片技术检测循环和转移的癌细胞。在某些肿瘤类型中,过表达与疾病的晚期和总体生存率降低有关,提示 EpCAM 作为一种潜在的预后标志物。除了其诊断和预后作用外,EpCAM 的广泛表达和明显参与肿瘤发生和转移表明其作为免疫治疗策略的潜在靶点。第一个靶向 EpCAM 的三功能抗体 catumaxomab(Removab®)在治疗 EpCAM 阳性癌相关恶性腹水方面显示出明显的临床益处。进一步的研究和临床研究应该阐明 EpCAM 在肿瘤发生过程中的复杂作用,并扩大 EpCAM 靶向策略的潜在治疗应用。