title: Molecular diagnosis of head and neck cancer.
abstract: Patients with advanced stages of head and neck cancer frequently develop locoregional recurrence as well as distant metastases. These data indicate that traditional diagnostic methods such as histopathology and radiology are not sensitive enough to detect the small numbers of tumor cells which are left behind, defined as minimal residual disease (MRD). Sensitive diagnostic assays based on molecular markers appear to be powerful tools to improve the staging of these patients. At the DNA level, tumor-specific p53 mutations seem to have great potential for the detection of "occult" tumor cells at surgical margins and lymph nodes. At the RNA level HNSCC associated antigens like the E48 antigen, allow the detection of rare HNSCC cells in blood and bone marrow and, it is hoped, also in lymph nodes and lymph node aspirates. However, the molecular assays which are used to detect MRD are subject to certain (technical) problems which affect their sensitivity and specificity. In this paper we will present examples of molecular assays such as the plaque assay using p53 mutations and the E48 RT-PCR, and show their use for MRD detection in cervical lymph nodes. In addition, we will discuss the problems and pitfalls associated with these sensitive techniques.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: V M
authors.initials: VM
authors.lastname: van Houten
authors.forename: M W
authors.initials: MW
authors.lastname: van den Brekel
authors.forename: F
authors.initials: F
authors.lastname: Denkers
authors.forename: D R
authors.initials: DR
authors.lastname: Colnot
authors.forename: J
authors.initials: J
authors.lastname: Westerga
authors.forename: P J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: G B
authors.initials: GB
authors.lastname: Snow
authors.forename: R H
authors.initials: RH
authors.lastname: Brakenhoff
mesh_terms: D016477:Artifacts; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005189:False Positive Reactions; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019914:Taq Polymerase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D018084:Ultrasonography, Interventional
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D019914:Taq Polymerase