Isogeneic comparison of primary and metastatic lung cancer identifies CX3CR1 as a molecular determinant of site-specific metastatic diffusion.

Metastatic diffusion is a major adverse prognostic determinant in lung cancer, that is ultimately responsible for significant morbidity, organ failure and death. Chemokine signaling pathways are known to guide site-specific metastatic spread in solid tumours. However, little is known about the contribution of CX3CR1 in the systemic dissemination of lung cancer. Syngeneic primary lung cancer/metastasis tissue microarray slides were constructed using 98 post-mortem specimens taken from patients with untreated lung cancer and immunostained for CX3CR1. Clinicopathological correlation between CX3CR1 expression and patient demographics, tumour histology, stage and pattern of metastatic spread was performed using χ2 test. CX3CR1 immunopositivity was significantly higher in non-small cell lung cancer (NSCLC) compared to small cell (SCLC) primary (p<0.001) and secondary tumours (p<0.001), with >75% of the metastatic sites staining positively in NSCLC. CX3CR1 positivity was significantly associated with stage and number of metastatic sites (p=0.03). At patients' death CX3CR1-negative lung adenocarcinomas were more likely to have spread to the brain and the liver (p=0.01). CX3CR1 is upregulated in NSCLC metastatic disease and its expression in primary lung tumours relates inversely to organotropic spread of cancer cells to the brain and the liver.