Metastasis Of Human Gastric Cancer Research Articles

Establishment and characterization of a new spontaneous metastasis model of human gastric carcinoma in nude mice.

A poorly differentiated medullary carcinoma of human stomach, designated HY–1, was successfully transplanted to nude mice by either the subcutaneous or intramuscular route for five generations. The transplanted tumor showed spontaneous lung metastases in nearly 100% of KSN and Balb/c female nude mice. There were over 20 visible lung metastatic nodules in KSN and Balb/c nude mice bearing tumors for over SO days. Immunostaining of type IV collagen and electron microscopy revealed that tumor cells were often in direct contact with basement membrane (BM) of tumor blood vessels in the primary tumor tissue. At the site of contact between tumor cells and vascular BM, focal disappearance of the BM, disruption of endothelial cells and entry of tumor cell clusters into vascular lumen were observed. Immunostaining of 72 kDa gelatinase/type IV collagenase demonstrated that tumor cells expressed this enzyme in their cytoplasm. These results suggest that spontaneous metastasis of this tumor may be partly due to a marked tendency to vascular invasion involving the following sequential events: tumor cell contact with vascular BM, BM degradation possibly by 72 kDa gelatinases and endothelial disruption. This model could be a useful tool for understanding the mechanism of hematogenous metastasis of human gastric cancer.

Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer

The infiltration of dendritic cells determined in 210 patients with gastric carcinoma was investigated from the standpoint of tumor invasion, lymph node metastasis, and prognosis. Dendritic cell infiltration was graded as "slight" and "marked." The 39% frequency in the marked infiltration group at the mucosal stage did not change in proportion to invasion into the deeper layers. The 5-year survival rate was 60.4% in patients with marked infiltration and 38.8% in those with slight infiltration, which was statistically different (P less than 0.01). The difference in survival rates was only statistically significant in those with cancer emerging from the serosa (P less than 0.001). There was a similar incidence of lymph node metastasis between the marked and slight infiltration groups in each grade of tumor invasion. However, marked infiltration of dendritic cells prevented widespread nodal involvement beyond the primary node in cases of advanced carcinoma (P less than 0.05). These findings indicate that infiltrating dendritic cells do not prevent the spread of tumor invasion but do prevent nodal involvement; therefore, for patients with a gastric cancer emerging from the serosa, the prognosis will be good.

The correlation of epidermal growth factor with invasion and metastasis in human gastric cancer

We examined the localization of epidermal growth factor (EGF) in 185 specimens of primary human gastric cancer using the avidin-biotin peroxidase complex immunohistochemical method on formalin-fixed paraffin-embedded sections. Thirty-four per cent of the gastric cancer specimens were positive for EGF, which was mainly located in the cytoplasm of the cancer cells and occasionally in the stromal cells, but was not detected in non-cancerous gastric epithelium. Moreover, the presence of EGF in gastric cancer was correlated with gastric wall invasion and lymph node metastasis. EGF was found more often in advanced cancers than in early ones (p less than 0.01), and also more often in cancers with lymph node metastasis than in those without (p less than 0.05). The five-year survival of patients with EGF-positive tumors was worse than that of patients with EGF-negative tumors (p less than 0.05). The presence of EGF in human gastric cancer may thus represent higher malignant potential.