Correlation between nm23 protein and several cell adhesion molecules in human gastric carcinoma

The correlation between nm23 protein (nm23) expression and the expression of several cell adhesion molecules was studied immunohistochemically in 110 resected gastric carcinomas. Formalin-fixed and paraffin-embedded samples were serially sectioned and stained with antibodies against nm23, integrin beta(1) subfamily members (alpha(2) beta(1), alpha(3) beta(1) and alpha(4) beta(1)), LFA-1, ICAM-1, sialyl Lewis(x) (sLe(x)) and CD44H, -V3, and -V6. Primary carcinomas presenting with either lymph node involvement or liver metastasis expressed significantly reduced levels of nm23 compared to tumors without metastasis. The percent of tumors expressing each adhesion molecule was as follows: alpha(2) beta(1), 27.3%; alpha(3) beta(1), 20.0%; alpha(4) beta(1), 14.5%; LFA-1, 14.5%; ICAM-1, 12.7%; sLe(x), 67.3%; CD44H, 55.5%; CD44v3, 20.0%; and CD44v6, 4.5%. Expression of alpha(2) beta(1) integrin and high levels of sLe(x) were significantly correlated with lymph node metastasis, and expression of alpha(3) beta(1) integrin and high levels of sLe(x) were correlated with liver metastasis. Expression of ICAM-1 was inversely correlated with liver metastasis. Comparing the expression of each cell adhesion molecule with nm23 immunoreactivity, expression of sLe(x) was significantly associated with nm23 expression. Of tumors expressing high levels of sLe(x), 75% showed reduced nm23 expression, compared to 52% of tumors with weak or no sLe(x) expression (P< 0.05). A similar tendency was also observed in the metastasized secondary tumors. These results suggest that reduced nm23 expression may promote the metastatic properties of cancer cells in concert with increased sLe(x) expression.