Background/aims: Lymph node metastases are thought to be formed as lymphatic flow, so the first metastasis is formed in the lymph node nearest the primary tumor and then further lymph node metastases are formed continuously down stream. In this study of gastric cancer, we evaluated whether IGF-2 (insulin-like growth factor-2), c-MET (hepatocyte growth factor receptor), MMP-7 (matrix metalloproteinase-7) and MUC-1, which are associated with nodal metastasis from primary tumor, are concerned with metastasis from nodal metastatic lesion to other nodes.
Methodology: Tissue specimens were obtained from 146 patients who underwent gastrectomy at the Department of Surgery II of Kanazawa University between 1989 and 1997. We evaluated the expression of IGF-2, c-MET, MMP-7 and MUC-1 in 146 primary tumors and 66 metastatic lymph nodes by immunohistological staining.
Results: In primary lesions, these 4 factors had significant association with lymphatic vessel infiltration and MMP-7 and MUC-1 had significant association with nodal metastases. In nodal metastatic lesions, positive rates of MMP-7 and MUC-1 were higher than in primary lesions. Furthermore, 37 (73%) of the 51 cases with positive staining for MMP-7 in metastatic lesions in perigastric lymph nodes and 5 (33%) of the 15 cases without the staining had nodal metastases in group 2 or more, showing significant difference (P < 0.05). And 37 (76%) of the 49 cases with positive staining for MUC-1 in metastatic lesions in perigastric lymph nodes and 5 (29%) of the 17 cases without the staining had nodal metastases in group 2 or more, showing significant difference (P < 0.01).
Conclusions: MMP-7 and MUC-1 were associated with not only nodal metastasis from primary tumor but also metastasis from nodal metastatic lesion to other nodes.