title: Clinical significance of micrometastatic cells detected by E48 (Ly-6D) reverse transcription-polymerase chain reaction in bone marrow of head and neck cancer patients.
abstract: OBJECTIVE
  Despite improvements in locoregional treatment of head and neck squamous cell carcinoma (HNSCC), local and distant failure rates remain high. The strongest prognostic indicator of HNSCC is the presence of lymph node metastases in the neck, but the value of this indicator has limitations when using for the individual patient. The presence of micrometastatic cells in bone marrow has been shown to be a putative prognostic indicator in HNSCC and other epithelial malignancies, which might allow more accurate staging and selection of patients for whom adjuvant or experimental therapy is recommended. The gene encoding the E48 antigen is selectively expressed by HNSCC, and the detection of E48 transcripts in bone marrow by reverse transcription-polymerase chain reaction (RT-PCR) presumably represents the presence of micrometastatic cells. The purpose of this study was to determine the association between the presence of micrometastatic cells in bone marrow of HNSCC patients and clinical outcome.
  
  
  METHODS
  A total of 162 patients treated surgically for primary HNSCC underwent a single bone marrow aspiration from the upper iliac crest for detection of micrometastatic cells using E48 RT-PCR. In total, 139 patients were evaluable. The primary statistical endpoints were disease-free survival and distant metastasis-free survival. In addition, bone marrow samples of 30 noncancer controls were evaluated.
  
  
  RESULTS
  E48 RT-PCR indicated the presence of micrometastatic cells in the bone marrow in 56 of 139 (40%) of the HNSCC patients and 0 of 30 of the noncancer controls (P < 0.0001). The presence of micrometastatic cells had no significant influence on disease-free survival or distant metastasis-free survival for the whole group of HNSCC patients (P = 0.1460 and P = 0.2912, respectively). For patients with >or=2 lymph node metastases, however, the presence of micrometastatic cells was associated with a poor distant metastasis-free survival (P = 0.0210).
  
  
  CONCLUSIONS
  The presence of micrometastatic cells in bone marrow of HNSCC patients with >or=2 lymph node metastases is correlated with a poor distant metastasis-free survival. In this subgroup of HNSCC patients, E48 RT-PCR seems to be a valuable tool to identify patients who are at increased risk for development of distant metastases and therefore might benefit from experimental adjuvant systemic therapy.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: David R
authors.initials: DR
authors.lastname: Colnot
authors.forename: Eline J C
authors.initials: EJ
authors.lastname: Nieuwenhuis
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Kuik
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
authors.forename: Janny
authors.initials: J
authors.lastname: Dijkstra
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Snow
authors.forename: Guus A M S
authors.initials: GA
authors.lastname: van Dongen
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
mesh_terms: D000950:Antigens, Ly / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000950:Antigens, Ly; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D006023:Glycoproteins; C094237:LY6D protein, human; D012333:RNA, Messenger