title: SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma.
abstract: BACKGROUND
  Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available.
  
  
  METHODS
  In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan-Meier survival analysis.
  
  
  RESULTS
  Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (P<0.001). ECS was associated with expression of either or both proteins in all cases. SMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (P<0.001). MRI showed poor sensitivity for detection of nodal metastasis (56%) and ECS (7%). Both separately, and in combination, SERPINE1 and SMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95%; SMA: 82%; combination: 81%).
  
  
  CONCLUSIONS
  A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.
authors.affiliation: Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: J
authors.initials: J
authors.lastname: Dhanda
authors.affiliation: 1] Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK [2] Regional Oral and Maxillofacial Unit, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Triantafyllou
authors.affiliation: Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: T
authors.initials: T
authors.lastname: Liloglou
authors.affiliation: Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: H
authors.initials: H
authors.lastname: Kalirai
authors.affiliation: Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: B
authors.initials: B
authors.lastname: Lloyd
authors.affiliation: Regional Oral and Maxillofacial Unit, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: R
authors.initials: R
authors.lastname: Hanlon
authors.affiliation: 1] Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK [2] Regional Oral and Maxillofacial Unit, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Shaw
authors.affiliation: Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Sibson
authors.affiliation: Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Risk
mesh_terms: D000199:Actins / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011379:Prognosis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human