Stoecklein Nikolas H, Siegmund Annika, Scheunemann Peter, Luebke Andreas M, Erbersdobler Andreas, Verde Pablo E, Eisenberger Claus F, Peiper Matthias, Rehders Alexander, Esch Jan Schulte Am, Knoefel Wolfram Trudo, Hosch Stefan B
Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Düsseldorf, D-40225 Düsseldorf, Germany.
BMC Cancer. 2006 Jun 23;6:165. doi: 10.1186/1471-2407-6-165.
To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies.
The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up.
Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor.
Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention.
评估上皮细胞粘附分子(Ep-CAM)在食管鳞状细胞癌(SCC)中的表达并检验其临床意义,以确定食管SCC患者是否适合接受Ep-CAM导向的靶向治疗。
使用单克隆抗体Ber-EP4对70例原发性食管SCC进行免疫组织化学研究,以检测Ep-CAM的表达。对于染色结果的解读,我们使用了从0到3+的标准化评分系统。对53例无远处转移、接受R0切除且至少有2个月临床随访的患者进行生存分析。
在79%的肿瘤中观察到Ep-CAM新表达,有三种表达水平,即1+(26%)、2+(11%)和3+(41%)。在所有表达水平均观察到异质性表达。有趣的是,Ep-CAM表达为3+的肿瘤的无复发生存期中位数显著缩短(对数秩检验,p = 0.0001),总生存期中位数也显著缩短(对数秩检验,p = 0.0003)。多因素生存分析显示Ep-CAM 3+表达是独立的预后因素。
我们的结果表明Ep-CAM是食管SCC靶向治疗中一个有吸引力的分子。考虑到目前食管SCC患者辅助治疗方案的不理想结果,Ep-CAM可能为辅助免疫治疗干预提供一个有前景的靶点。