Correlation between nm23 Protein and Several Cell Adhesion Molecules in Human Gastric Carcinoma

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Abstract
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 β1 subfamily members (α2β1, α3β1 and α4β1), LFA‐1, ICAM‐1, sialyl Lewisx (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: α2β1, 27.3%; α3β1, 20.0%; α4β1, 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 α2β1 integrin and high levels of sLex were significantly correlated with lymph node metastasis, and expression of α3β1 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.