Gene analysis and elucidation of mechanism of implantation and growth of lymph node micrometastasis in gastrointestinal cancer

淋巴结转移是影响胃肠道肿瘤预后的因素之一。我们报道了胃肠道肿瘤淋巴结微转移的临床意义。虽然淋巴结微转移在形态学上分为集群型和单细胞型，但这种转移是否会植入和生长尚不清楚。近年来，在胃肠道肿瘤中引入了先接受原发肿瘤淋巴流的前哨淋巴结（sentinel node， SN）的概念。食管癌和胃癌早期SN几乎有淋巴结转移，包括微转移。用专门对淋巴管起反应的D2-40抗体对淋巴浸润进行详细观察，淋巴浸润阳性患者的淋巴结微转移率明显高于淋巴浸润阴性患者。因此，淋巴浸润的详细检查有助于预测淋巴结转移，包括微转移。通过Ki-67的表达分析微转移瘤的增殖活性。Ki-67在大小大于0.2 mm和小于0.2 mm的淋巴结转移中的阳性表达率分别为90%和29%。因此，即使在微转移中也发现了增殖活性，这种转移应予以治疗。血管生成和趋化因子CXCL12在淋巴结转移（包括微转移）患者中均呈阳性表达。术前放化疗患者的淋巴结微转移发生率明显低于单纯手术患者。特别是术前放化疗患者，未发现单细胞型微转移。然而，由于在放化疗无效的患者中发现了群集型微转移，因此需要进一步治疗。本研究结果为探讨肿瘤淋巴转移的机制和治疗策略提供了有益的信息。少

Lymph node metastasis is one of the prognostic factors in gastrointestinal cancer. We have reported the clinical significance of lymph node micrometastasis in gastrointestinal cancer. Although lymph node micrometastasis is morphologically divided into cluster type and single cell type, it is still unknown whether such metastases implant and grow. Recently, the concept of sentinel node (SN)which firstly receives the lymphatic flow from primary tumor has been introduced in gastrointestinal cancer. Almost lymph node metastasis, including micrometastasis was found in SN in the early stage of esophageal and gastric carcinomas. When the detailed lymphatic invasion was observed by D2-40 antibody which specially reacts for lymphatic vessels, lymph node micrometastasis is significantly higher in patients with positive lymphatic invasion than in those with negative lymphatic invasion. Thus, detailed examination of lymphatic invasion is useful for predicting the lymph node metastasis, including m … More icrometastasis. We analyzed the proliferative activity of micrometastasis by Ki-67 expression. The percentage of Ki-67 positive expression in nodal metastases with more than 0.2 mm in size and with less than 0.2 mm in size was 90% and 29%, respectively. Therefore, proliferative activity was found even in micrometastasis, such metastasis should be treated. The positive expression of angiogenesis and CXCL12 which is one of the chemokines was found in patients with nodal metastasis, including micrometastasis. The incidence of lymph node micrometastasis was significantly lower in patients with preoperative chemoradiation therapy than in those with surgery alone. Especially in patients with preoperative chemoradiation therapy, the micrometastasis with single cell type was not found. However, since the micrometastasis with cluster type was found in patients with ineffective response for chemoradiation therapy, further treatment should be necessary. In conclusion, the results obtained from this study offer the useful information for the mechanism of lymphatic metastasis and for treatment strategy. Less