Loss of β-arrestin-2 and Activation of CXCR2 Correlate with Lymph Node Metastasis in Non-small Cell Lung Cancer.

: Although β-arrestin-2 (β-arr2) and CXCR2 have been shown to affect various malignant tumors, their exact roles in lung cancer remain unclear. We investigated expression of β-arr2 and CXCR2 in patients with non-small cell lung cancer (NSCLC) and their correlation with lymph node metastasis and prognosis. : We reviewed medical records of 136 patients with NSCLC who underwent surgical resection, and assessed their specimens immunohistochemically for expression of β-arr2 and CXCR2 in primary tumors and metastatic lymph nodes (MLNs), respectively. High β-arr2 expression was seen in 63 specimens (46.3%), and was significantly associated with male patients (=0.011), squamous cell carcinoma (=0.003), and lymph node metastasis (<0.001). High CXCR2 expression was seen in 62 specimens (45.6%), and was significantly correlated only with lymph node metastasis (<0.001). Expression of β-arr2 was significantly lower at MLNs than at primary lesions (=-2.315; 0.021; Wilcoxon signed-rank), whereas CXCR2 expression was significantly higher in MLNs than in primary lesions (=-3.712; 0.001; Wilcoxon signed-rank). No relationship was seen between β-arr2 and CXCR2 expression in primary lesions (=-0.065, =0.548; Spearman rank coefficient), but they were inversely related in MLNs (=-0.263, =0.012). Kaplan-Meier survival curve was shown that low β-arr2 and high CXCR2 expressions was associated with poor survival (log-rank: =5.926, =0.015). : β-arr2 may promote lymph node metastasis in NSCLC by modulating CXCR2 activation.