title: Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) in squamous cell carcinoma of the tongue: markers of nerve invasion?
abstract: OBJECTIVE
  Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is an independent predictor of poor prognosis. As PNI is not always identified with routine histology, a surrogate marker of PNI would improve detection and better inform treatment planning. The chemokines fractalkine (CX3CL1) and its receptor (CX3CR1) have shown such potential in other cancers, but have yet to be investigated with respect to PNI in oral SCC.
  
  
  METHODS
  Thirty SCCs of the tongue in which PNI was identified histologically, and 30 in which it was not, were stained for fractalkine and fractalkine receptor using polyclonal antibodies and an immunoperoxidase technique. Tumours were assessed as either positive or negative; no attempt was made to subjectively assess staining intensity or extent.
  
  
  RESULTS
  Both markers labelled myofibroblasts in the stroma surrounding the tumour, various neural components, leucocytes, endothelium and salivary myoepithelial cells. Fractalkine also labelled salivary ductal epithelium, vascular smooth muscle and 12/30 SCC which showed PNI. Eight of 30 positive SCCs in which PNI was not identified were also positive for this marker. There was no statistically significant association between fractalkine staining and PNI (p = 0.273). No SCC was positive for fractalkine receptor, but immune dendritic cells within tumour islands were strongly positive, as was striated muscle.
  
  
  CONCLUSIONS
  Neither fractalkine nor fractalkine receptor is a reliable surrogate marker of PNI in lingual SCC.
authors.affiliation: Queen Victoria Hospital NHSF Trust, East Grinstead, West Sussex, UK.
authors.forename: S
authors.initials: S
authors.lastname: Doumas
authors.forename: J C
authors.initials: JC
authors.lastname: Paterson
authors.forename: P M
authors.initials: PM
authors.lastname: Norris
authors.forename: J V
authors.initials: JV
authors.lastname: Tighe
authors.forename: L
authors.initials: L
authors.lastname: Newman
authors.forename: B S
authors.initials: BS
authors.lastname: Bisase
authors.forename: A E
authors.initials: AE
authors.lastname: Kolokotronis
authors.forename: A W
authors.initials: AW
authors.lastname: Barrett
mesh_terms: D015415:Biomarkers / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D000073883:CX3C Chemokine Receptor 1; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D054428:Chemokine CX3CL1 / Q000032:analysis*; D006801:Humans; D058628:Myofibroblasts / Q000473:pathology; D009361:Neoplasm Invasiveness; D010525:Peripheral Nerves / Q000473:pathology*; D011379:Prognosis; D019707:Receptors, Chemokine / Q000032:analysis*; D014062:Tongue Neoplasms / Q000473:pathology*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine