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

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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