title: Isogeneic comparison of primary and metastatic lung cancer identifies             CX3CR1 as a molecular determinant of site-specific metastatic diffusion.
abstract: 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.
authors.affiliation: Department of Histopathology, Imperial College London, Hammersmith Campus, and Department of Respiratory Medicine, Hammersmith Hospital, London, UK. f.mauri@imperial.ac.uk
authors.forename: Francesco A
authors.initials: FA
authors.lastname: Mauri
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinato
authors.forename: Pritesh
authors.initials: P
authors.lastname: Trivedi
authors.forename: Rohini
authors.initials: R
authors.lastname: Sharma
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Shiner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary*; D000073883:CX3C Chemokine Receptor 1; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D054428:Chemokine CX3CL1 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine