title: Prognostic molecular markers in head and neck squamous cell carcinoma in a New Zealand population: matrix metalloproteinase-2 and sialyl Lewis x antigen.
abstract: OBJECTIVE
  The survival rate for head and neck squamous cell carcinoma (HNSCC) is among the lowest of the major cancers and has not substantially improved in the past two decades. Tumours with similar histological features may have widely differing clinical outcomes and thus identification of prognostic and predictive biomarkers may be valuable for determining appropriate clinical management strategies. The objective of this study was to establish the prognostic significance of six molecular markers in HNSCC in a New Zealand population: matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinase-1, sialyl Lewis antigens a and x (sLe(a) , sLe(x) ) and alpha B-crystallin.
  
  
  METHODS
  Retrospective review of 145 sequential HNSCC patients from a tertiary centre with minimum 3 years surveillance. Sections from formalin-fixed paraffin-embedded tumour blocks were immunostained for the molecular markers and scored. Cox regression modelling was used to adjust for potential confounding variables impacting on cancer survival.
  
  
  RESULTS
  Multivariate analysis for individual biomarkers, controlling for age, sex, tumour grade, N-stage, T-stage, tumour site, smoking history and alcohol use, revealed poorer survival with tumour expression of MMP-2 (hazard ratio = 1.98, 95% confidence interval: 1.11-3.52, P = 0.021) and sLe(x) (hazard ratio = 3.22, 95% confidence interval: 1.33-7.80, P = 0.010). A stepwise analysis showed that MMP-2 and sLe(x) were independently prognostic after covariate adjustment.
  
  
  CONCLUSIONS
  MMP-2 and sLe(x) were negative prognostic markers for survival in these HNSCC patients. This offers opportunities for clinical trials to reduce the risk of nodal and distant metastases through blocking tumour cell adhesion to endothelium.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Waikato Hospital, Hamilton, New Zealand.
authors.forename: Indunil
authors.initials: I
authors.lastname: Gunawardena
authors.affiliation: Department of Pathology, Waikato Hospital, Hamilton, New Zealand.
authors.forename: Michael
authors.initials: M
authors.lastname: Arendse
authors.affiliation: Regional Cancer Centre, Waikato Hospital, Hamilton, New Zealand.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jameson
authors.affiliation: Department of Surgery, University of Auckland, Auckland, New Zealand.
authors.forename: Lindsay D
authors.initials: LD
authors.lastname: Plank
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Waikato Hospital, Hamilton, New Zealand.
authors.forename: R Theo
authors.initials: RT
authors.lastname: Gregor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018395:CA-19-9 Antigen; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D016256:Lewis X Antigen / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009520:New Zealand; D009844:Oligosaccharides / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000080506:Sialyl Lewis X Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D016256:Lewis X Antigen; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1; D038203:alpha-Crystallin B Chain; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: head and neck squamous cell carcinoma; matrix metalloproteinase; molecular marker; prognostic markers; sialyl Lewis x antigen