Spizzo Gilbert, Went Philip, Dirnhofer Stephan, Obrist Peter, Simon Ronald, Spichtin Hanspeter, Maurer Robert, Metzger Urs, von Castelberg Brida, Bart Rahel, Stopatschinskaya Shanna, Köchli Ossi Robert, Haas Philip, Mross Friedrich, Zuber Markus, Dietrich Holger, Bischoff Susanne, Mirlacher Martina, Sauter Guido, Gastl Guenther
Division of Haematology and Oncology, University of Innsbruck, Innsbruck, Austria.
Breast Cancer Res Treat. 2004 Aug;86(3):207-13. doi: 10.1023/B:BREA.0000036787.59816.01.
Previous studies in small series of patients with invasive breast cancer suggested a prognostic value of Ep-CAM overexpression in primary tumor tissue. To corroborate these findings, we performed a retrospective analysis of Ep-CAM expression using a tissue microarray containing tissue specimens from a large patient set. Ep-CAM expression was evaluated by immunohistochemistry in breast cancer tissue from 1715 patients with documented raw survival data. High level Ep-CAM expression (overexpression) was found in 41.7% of tumor samples, low level expression was found in 48.0% and no expression in 10.3% of tumor samples. Ep-CAM expression predicted poor overall survival in this patient cohort (p < 0.0001). Overall survival decreased significantly with increasing Ep-CAM expression. However, in this patient sample Ep-CAM expression was not an independent prognostic marker by multivariate analysis. Subgroup analysis revealed that Ep-CAM expression was a prognostic marker in node-positive (p < 0.0001) but not in node-negative (p = 0.58) breast cancer patients. Intriguingly, Ep-CAM expression was predictive for a dismal prognosis in patients receiving adjuvant cytotoxic (p = 0.03) or hormonal therapy (p < 0.0001) but not in untreated patients (p = 0.41). In summary, this study provides strong evidence that expression of Ep-CAM is a powerful marker of poor prognosis in node-positive invasive breast carcinoma and a potential predictive marker of sensitivity to adjuvant hormonal and/or cytotoxic treatment modalities.
先前针对一小部分浸润性乳腺癌患者的研究表明，上皮细胞黏附分子（Ep-CAM）在原发性肿瘤组织中的过表达具有预后价值。为了证实这些发现，我们使用包含大量患者组织样本的组织微阵列对Ep-CAM表达进行了回顾性分析。通过免疫组织化学对1715例有原始生存数据记录的乳腺癌患者的组织进行Ep-CAM表达评估。在41.7%的肿瘤样本中发现高水平Ep-CAM表达（过表达），48.0%的肿瘤样本中发现低水平表达，10.3%的肿瘤样本中未发现表达。在该患者队列中，Ep-CAM表达预示着总体生存率较差（p<0.0001）。总体生存率随着Ep-CAM表达的增加而显著降低。然而，在该患者样本中，通过多变量分析，Ep-CAM表达并非独立的预后标志物。亚组分析显示，Ep-CAM表达在淋巴结阳性乳腺癌患者中是预后标志物（p<0.0001），而在淋巴结阴性乳腺癌患者中则不是（p = 0.58）。有趣的是，Ep-CAM表达对接受辅助细胞毒性治疗（p = 0.03）或激素治疗（p<0.0001）的患者的不良预后具有预测性，但对未接受治疗的患者则无此作用（p = 0.41）。总之，本研究提供了有力证据，表明Ep-CAM表达是淋巴结阳性浸润性乳腺癌预后不良的有力标志物，也是对辅助激素和/或细胞毒性治疗方式敏感性的潜在预测标志物。
