Department of General, Visceral, and Paediatric Surgery, University Hospital Dusseldorf, 40225 Düsseldorf, Germany.
Am J Surg Pathol. 2012 Dec;36(12):1809-16. doi: 10.1097/PAS.0b013e318265288c.
Here we evaluated the prevalence and prognostic impact of epithelial cell adhesion molecule (EpCAM)-positive disseminated tumor cells (DTCs) in stage I rectal cancer. Further we tested the association of these single tumor cells or small tumor cell groups with the extent of peritumoral lymphangiogenesis. A total of 845 regional lymph nodes (LN) of 44 patients classified as negative on conventional histopathology were retrospectively reanalyzed with immunohistochemistry (IHC) using the monoclonal antibody Ber-Ep4 directed against EpCAM for the detection of DTCs. The degree of lymphangiogenesis in the primary tumors was assessed by IHC of the primary tumor tissue using the monoclonal antibody D2-40, which reacts with the lymphatic endothelium. The IHC results were correlated with clinico-pathologic parameters and clinical follow-up data. EpCAM-positive DTCs in LNs were detected in 8 (18.2%) of the 44 patients. During a median follow-up of 59 months, 3 (37.5%) of the 8 patients with EpCAM-positive DTCs relapsed, whereas none of the DTC-negative patients developed tumor recurrence (P=0.004). Survival analysis revealed a significant effect of the prevalence of DTCs on overall survival (P=0.0009) and on recurrence-free survival (P=0.0001). Finally, the prevalence of EpCAM-positive DTCs in perirectal LNs was significantly correlated with a high density of peritumoral lymphatic vessels (P=0.015). Our results show that DTCs may occur in stage I of rectal cancer and are associated with poor prognosis. Their occurrence seems to be linked to a high density of newly formed lymphatic vessel at the primary tumor site. According to our data, patients with DTCs in their LN might benefit from adjuvant therapy.
在这里，我们评估了Ⅰ期直肠癌中上皮细胞黏附分子（EpCAM）阳性播散性肿瘤细胞（DTCs）的发生率和预后影响。进一步，我们检测了这些单个肿瘤细胞或小肿瘤细胞群与肿瘤周围淋巴管生成程度的关联。总共对 44 名患者的 845 个区域淋巴结（LN）进行了回顾性重新分析，这些患者在常规组织病理学上均为阴性，使用针对 EpCAM 的单克隆抗体 Ber-Ep4 进行免疫组织化学（IHC）检测以检测 DTCs。通过使用与淋巴管内皮反应的单克隆抗体 D2-40 对原发性肿瘤组织进行 IHC 评估原发性肿瘤中的淋巴管生成程度。IHC 结果与临床病理参数和临床随访数据相关。在 44 名患者中，有 8 名（18.2%）患者的 LN 中检测到 EpCAM 阳性 DTCs。在中位数为 59 个月的随访期间，8 名 EpCAM 阳性 DTC 患者中有 3 名（37.5%）复发，而无 DTC 阴性患者发生肿瘤复发（P=0.004）。生存分析显示 DTCs 的发生率对总生存（P=0.0009）和无复发生存（P=0.0001）有显著影响。最后，直肠周围 LN 中 EpCAM 阳性 DTCs 的发生率与肿瘤周围淋巴管密度高显著相关（P=0.015）。我们的结果表明，DTCs 可能发生在直肠癌的Ⅰ期，并与不良预后相关。它们的发生似乎与原发性肿瘤部位新生淋巴管密度高有关。根据我们的数据，LN 中有 DTCs 的患者可能受益于辅助治疗。
