Cellular Oncology

, Volume 35, Issue 5, pp 367–375 | Cite as

Molecular diagnosis of minimal residual disease in head and neck cancer patients

  • A. Peggy Graveland
  • Boudewijn J. M. Braakhuis
  • Simone E. J. Eerenstein
  • Remco de Bree
  • Elisabeth Bloemena
  • Michiel de Maaker
  • Michiel W. M. van den Brekel
  • Frederike Dijk
  • Wilma E. Mesker
  • Hans J. Tanke
  • C. Rene Leemans
  • Ruud H. Brakenhoff
Original Paper



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.


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.


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.


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.


Minimal residual cancer Bone marrow Head and neck cancer Non-cohesive growth Molecular diagnosis Vaso-invasive growth 


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Copyright information

© International Society for Cellular Oncology 2012

Authors and Affiliations

  • A. Peggy Graveland
    • 1
  • Boudewijn J. M. Braakhuis
    • 1
  • Simone E. J. Eerenstein
    • 1
  • Remco de Bree
    • 1
  • Elisabeth Bloemena
    • 2
    • 3
  • Michiel de Maaker
    • 1
  • Michiel W. M. van den Brekel
    • 4
  • Frederike Dijk
    • 1
  • Wilma E. Mesker
    • 5
  • Hans J. Tanke
    • 6
  • C. Rene Leemans
    • 1
  • Ruud H. Brakenhoff
    • 1
  1. 1.Department of Otolaryngology/Head and Neck SurgeryVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of PathologyVU University Medical CenterAmsterdamThe Netherlands
  3. 3.Department of Oral and Maxillofacial Surgery/Oral PathologyAcademic Centre of Dentistry Amsterdam (ACTA)AmsterdamThe Netherlands
  4. 4.Department of Head and Neck Oncology and SurgeryNetherlands Cancer Institute/Antoni van Leeuwenhoek Hospital and Institute of Phonetic Sciences University of Amsterdam (ACLC)AmsterdamThe Netherlands
  5. 5.Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
  6. 6.Department of Molecular Cell BiologyLeiden University Medical CenterLeidenThe Netherlands

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