title: Molecular diagnosis of minimal residual disease in head and neck cancer patients.
abstract: OBJECTIVE
  Locoregional recurrences and distant metastases in adequately treated head and neck squamous cell carcinoma (HNSCC) patients have a dismal effect on survival. Tumor cells that escape histopathological detection might be the prime cause of this effect. We evaluated whether minimal residual cancer (MRC) in deep surgical margins and disseminated tumor cells (DTCs) in bone marrow aspirates are associated with clinicohistopathological parameters and outcome.
  
  
  METHODS
  Submucosal samples of deep resection margins of 105 HNSCC patients with histopathologically tumor-free surgical margins were analysed for the presence of MRC using hLy-6D qRT-PCR. Bone-marrow aspirates of 76 of these patients were analysed for DTCs by immunocytochemical staining. Presence of molecular-positive deep surgical margins, presence of DTC in bone marrow aspirates, and clinicohistopathological parameters were tested for associations with survival parameters by univariate and multivariate analyses.
  
  
  RESULTS
  In addition to lymph node stage, it appeared that vasoinvasive growth and particularly infiltrative growth pattern are significant predictors for locoregional recurrence (p = 0.041 and p = 0.006, respectively) and disease-free survival (p = 0.014 and p = 0.008, respectively). Remarkably, neither the presence of molecular-positive deep surgical margins nor that of DTC in bone marrow aspirates were significantly related to outcome.
  
  
  CONCLUSIONS
  The presence of vasoinvasive and infiltrative growth in HNSCC tumor specimens are significant risk-factors for locoregional recurrence and disease-free survival. At present there seems no role for molecular analysis of deep surgical margins and bone marrow aspirates in predicting outcome with the methods used.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: A Peggy
authors.initials: AP
authors.lastname: Graveland
authors.forename: Boudewijn J M
authors.initials: BJ
authors.lastname: Braakhuis
authors.forename: Simone E J
authors.initials: SE
authors.lastname: Eerenstein
authors.forename: Remco
authors.initials: R
authors.lastname: de Bree
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
authors.forename: Michiel
authors.initials: M
authors.lastname: de Maaker
authors.forename: Michiel W M
authors.initials: MW
authors.lastname: van den Brekel
authors.forename: Frederike
authors.initials: F
authors.lastname: Dijk
authors.forename: Wilma E
authors.initials: WE
authors.lastname: Mesker
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Tanke
authors.forename: C Rene
authors.initials: CR
authors.lastname: Leemans
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D016016:Proportional Hazards Models; D013194:Staining and Labeling; D055815:Young Adult