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CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer.

The chemokine receptors CCR7 and CXCR4 play a major role in the mechanism of lymph node metastasis from primary tumor cells. We postulated that their expression in gastric tumor cells could predict lymph node status including lymph node micrometastasis (LNMM). We assessed CCR7 and CXCR4 expression in 93 resected gastric tumor specimens by immunohistochemistry. Dissected lymph nodes were examined by reverse transcription-polymerase chain reaction and immunohistochemistry using cytokeratin monoclonal antibody to detect LNMM in addition to hematoxylin-eosin (H&E) staining. Levels of CCR7 and CXCR4 expression were high in 26.9% (25/93) and in 32.3% (30/93), respectively of tumor cells and the levels significantly correlated with lymph node metastasis according to H&E staining (P=0.0212 and P=0.0115, respectively). We identified LNMM in 25 of 83 (30.1%) node-negative patients. Both CCR7 and CXCR4 expression significantly correlated with lymph node status including LNMM (P=0.0092 and P=0.0075, respectively). Furthermore, levels of combined CCR7 and CXCR4 expression significantly correlated with lymph node metastatic status (P=0.0021). Assessment of CCR7 and CXCR4 expression in gastric cancer is a useful tool for predicting lymph node metastatic status including LNMM.