Tumor angiogenesis and micrometastasis in bone marrow of patients with early gastric cancer

In a subset of patients with early gastric cancer, there were recurrences of the disease after a curative resection had been done. Direct evidence of tumor seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap because it is a feature of epithelial cells that would not normally be present in bone marrow. From 1994-1997, the bone marrow of 45 patients with early gastric cancer was examined for tumor cells, using immunocytochemical techniques and an antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. Intratumoral microvessels were stained with anti-CD31 monoclonal antibody. Clinicopathological characteristics were determined for subjects with cytokeratin-positive cells in the bone marrow. Of these 45 patients, 9 (20.0%) had cytokeratin-positive cells in the bone marrow at the time of primary surgery. These positive findings were not related to tumor advance-related factors of lymph node metastasis and distinct lymphatic and vascular invasion. Microvessel density in the primary tumor exceeded 2-fold in cytokeratin-positive cells, compared with findings in negative cells (P < 0.05). Tumor cells in bone marrow are indicative of the general disseminative metastasis in patients with early gastric cancer, and the metastatic potential was closely related to angiogenesis in the primary tumor.