Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy
Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy
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DOI：
10.1111/igc.0b013e3181a8331f
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发表时间：
2009-07-01
影响因子：
4.8
通讯作者：
Santin, Alessandro D.
中科院分区：
文献类型：
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作者：
Bellone, Stefania;Siegel, Eric R.;Santin, Alessandro D.
为了评价上皮细胞黏附分子(EP-CAM/trop-1)特异性免疫治疗上皮性卵巢癌(EOCs)的可能性，我们从RNA和蛋白水平分析了Ep-CAM在原发、转移和化疗耐药/复发卵巢癌(EOC)患者中的表达。应用实时定量聚合酶链式反应和免疫组织化学方法检测168例新鲜冰冻组织和石蜡包埋组织中上皮细胞黏附分子的表达。此外，在体内和体外，用流式细胞术对几个新建立的卵巢癌细胞株的EP-CAM表面表达进行了评估，这些细胞系来自于对化疗有耐药性的肿瘤患者。与正常卵巢表面细胞系和新鲜冷冻的正常卵巢组织相比，原发、转移和复发卵巢癌组织中上皮细胞黏附分子转录本的表达显著升高(P<；0.001)。同样，通过免疫组织化学方法发现，EP-CAM蛋白在原发、转移和复发卵巢癌组织中的表达显著高于正常卵巢组织。值得注意的是，与原发卵巢癌相比，转移性/复发性肿瘤的EP-CAM蛋白表达水平显著升高(P<；0.001)。最后，流式细胞仪检测发现100%(5/5)的卵巢癌细胞株表面高表达EP-CAM。这些结果表明EP-CAM在卵巢癌中高表达，特别是在转移性和复发/化疗耐药的卵巢疾病中。EP-CAM在腹膜腔内的螯合上皮细胞上缺乏表达，再加上最近研制的全人抗EP-CAM表面分子的单抗，提示EP-CAM有望成为卵巢癌患者抗体介导治疗的靶点，这些患者的肿瘤对标准治疗方案无效。
To evaluate the potential of epithelial cell adhesion molecule (Ep-CAM/TROP-1)-specific immunotherapy against epithelial ovarian carcinomas (EOCs), we have analyzed the expression of Ep-CAM at RNA and protein level in patients harboring primary, metastatic, and chemotherapy-resistant/recurrent EOC. Epithelial cell adhesion molecule expression was evaluated by real-time polymerase chain reaction and immunohistochemistry in 168 fresh-frozen biopsies and paraffin-embedded tissues. In addition, Ep-CAM Surface expression was evaluated by flow cytometry in several freshly established ovarian carcinoma cell lines derived from patients harboring tumors resistant to chemotherapy in vivo as well as in vitro. Epithelial cell adhesion molecule transcript was found significantly overexpressed in primary, metastatic, and recurrent EOC when compared with normal human ovarian surface epithelium cell lines and fresh-frozen normal ovarian tissue (P < 0.001). Similarly, by immunohistochemistry, Ep-CAM protein expression was found significantly higher in primary, metastatic, and recurrent EOC when compared with normal ovarian tissues. Of interest, metastatic/recurrent tumors were found to express significantly higher levels of Ep-CAM protein when compared with primary ovarian carcinomas (P < 0.001). Finally, a high surface expression of Ep-CAM was found in 100% (5/5) of the chemotherapy-resistant ovarian carcinoma cell lines studied by flow cytometry. These results demonstrate high Ep-CAM overexpression in ovarian carcinoma, especially in metastatic and recurrent/chemotherapy-resistant ovarian disease. The lack of Ep-CAM expression on the chelomic epithelium in the peritoneal cavity, combined with the recent development of fully human monoclonal antibodies against this Surface molecule, Suggest Ep-CAM as a promising target for antibody-mediated therapies in ovarian carcinoma patients harboring tumors refractory to standard treatment modalities.