Department of General, Institute of Pathology, University Hospital of the Heinrich-Heine University Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Eur J Endocrinol. 2010 Feb;162(2):391-8. doi: 10.1530/EJE-08-0916.
EpCAM (CD326) is overexpressed in progenitor cells of endocrine pancreatic islands of Langerhans during fetal development and was suggested to act as a morphoregulatory molecule in pancreatic island ontogeny. We tested whether EpCAM overexpression is reactivated in insulinomas, endocrine tumors arising in the pancreas.
DESIGN/METHOD: We used monoclonal anti-EpCAM antibody Ber-Ep4 for immunohistochemistry on formalin-fixed and paraffin-embedded tumor material. We analyzed 53 insulinomas: 40 benign (disease stage<IIa) and 13 malignant tumors (disease stage IIIb/IV). Disease stage disposition followed new TNM classification of the European Neuroendocrine Tumor Society (ENETS) for foregut neuroendocrine tumors (2006). Additionally, ten insulinoma metastases were analyzed. Clinical follow-up was available for overall survival analysis from 49 patients. The EpCAM expression of the islands of Langerhans was classified as 2+ in healthy pancreatic tissue.
In 38% of the benign insulinomas (disease stage<IIa), we found strong (3+) EpCAM expression. In contrast, malignant insulinomas (disease stage IIIb/IV) and their metastases exhibited a strong (3+) EpCAM expression with 78 and 80% respectively, significantly more frequent (P<0.01). The malignant tissue was characterized by a significantly lower number of unstained cells and significantly higher number of 3+ stained cells. Quantitative PCR for EpCAM mRNA validated strong EpCAM expression in malignant insulinoma. Kaplan-Meier curves indicated survival disadvantage for EpCAM 3+ insulinomas, but this was not statistically significant (log-rank test).
This first EpCAM expression study in benign/malignant insulinomas indicates that strong EpCAM expression could help to identify patients at risk for malignant disease and might be used as a therapeutic target for antibody-based therapies in patients with metastatic insulinoma.
EpCAM（CD326）在胰岛的祖细胞中过表达，在胰岛的发生发育中可能作为一种形态调节分子。我们检测 EpCAM 的过表达是否在胰岛素瘤中重新激活，胰岛素瘤是发生于胰腺的内分泌肿瘤。
设计/方法：我们应用单克隆抗 EpCAM 抗体 Ber-Ep4 对福尔马林固定石蜡包埋的肿瘤组织进行免疫组化染色。我们分析了 53 例胰岛素瘤：40 例良性（疾病分期<IIa）和 13 例恶性肿瘤（疾病分期 IIIb/IV）。疾病分期依据欧洲神经内分泌肿瘤学会（ENETS）新的用于前肠神经内分泌肿瘤（2006）的 TNM 分类。另外，我们分析了 10 例胰岛素瘤转移灶。49 例患者的临床随访资料可用于总生存分析。在健康胰腺组织中胰岛的 EpCAM 表达被定义为 2+。
在 38%的良性胰岛素瘤（疾病分期<IIa）中，我们发现强（3+）EpCAM 表达。相比之下，恶性胰岛素瘤（疾病分期 IIIb/IV）及其转移灶分别显示出强（3+）EpCAM 表达，分别为 78%和 80%，表达明显更频繁（P<0.01）。恶性组织的特征是未染色细胞的数量明显减少，而 3+染色细胞的数量明显增加。EpCAM mRNA 的定量 PCR 验证了恶性胰岛素瘤中 EpCAM 的强表达。Kaplan-Meier 曲线表明 EpCAM 3+胰岛素瘤患者的生存劣势，但无统计学意义（对数秩检验）。
这是首次在良性/恶性胰岛素瘤中进行 EpCAM 表达研究，表明强 EpCAM 表达有助于识别恶性疾病风险患者，可能作为转移性胰岛素瘤患者基于抗体的治疗的治疗靶点。
