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 beta1 subfamily members (alpha2beta1, alpha3beta1 and alpha4beta1), LFA-1, ICAM-1, sialyl Lewis(x) (sLex) 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: alpha2beta1, 27.3%; alpha3beta1, 20.0%; alpha4beta1, 14.5%; LFA-1, 14.5%; ICAM-1, 12.7%; sLex, 67.3%; CD44H, 55.5%; CD44V3, 20.0%; and CD44V6, 4.5%. Expression of alpha2beta1 integrin and high levels of sLex were significantly correlated with lymph node metastasis, and expression of alpha3beta1 integrin and high levels of sLex 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 sLex was significantly associated with nm23 expression. Of tumors expressing high levels of sLex, 75% showed reduced nm23 expression, compared to 52% of tumors with weak or no sLex 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 sLex expression.