title: DSG3 as a biomarker for the ultrasensitive detection of occult lymph node metastasis in oral cancer using nanostructured immunoarrays.
abstract: OBJECTIVE
  The diagnosis of cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) patients constitutes an essential requirement for clinical staging and treatment selection. However, clinical assessment by physical examination and different imaging modalities, as well as by histological examination of routine lymph node cryosections can miss micrometastases, while false positives may lead to unnecessary elective lymph node neck resections. Here, we explored the feasibility of developing a sensitive assay system for desmoglein 3 (DSG3) as a predictive biomarker for lymph node metastasis in HNSCC.
  
  
  METHODS
  DSG3 expression was determined in multiple general cancer- and HNSCC-tissue microarrays (TMAs), in negative and positive HNSCC metastatic cervical lymph nodes, and in a variety of HNSCC and control cell lines. A nanostructured immunoarray system was developed for the ultrasensitive detection of DSG3 in lymph node tissue lysates.
  
  
  RESULTS
  We demonstrate that DSG3 is highly expressed in all HNSCC lesions and their metastatic cervical lymph nodes, but absent in non-invaded lymph nodes. We show that DSG3 can be rapidly detected with high sensitivity using a simple microfluidic immunoarray platform, even in human tissue sections including very few HNSCC invading cells, hence distinguishing between positive and negative lymph nodes.
  
  
  CONCLUSIONS
  We provide a proof of principle supporting that ultrasensitive nanostructured assay systems for DSG3 can be exploited to detect micrometastatic HNSCC lesions in lymph nodes, which can improve the diagnosis and guide in the selection of appropriate therapeutic intervention modalities for HNSCC patients.
authors.affiliation: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4330, USA.
authors.forename: Vyomesh
authors.initials: V
authors.lastname: Patel
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.forename: Ruchika
authors.initials: R
authors.lastname: Malhotra
authors.forename: Christina A
authors.initials: CA
authors.lastname: Marsh
authors.forename: Colleen L
authors.initials: CL
authors.lastname: Doçi
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Cherie-Ann O
authors.initials: CA
authors.lastname: Nathan
authors.forename: Uttam K
authors.initials: UK
authors.lastname: Sinha
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Molinolo
authors.forename: James F
authors.initials: JF
authors.lastname: Rusling
authors.forename: J Silvio
authors.initials: JS
authors.lastname: Gutkind
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D051184:Desmoglein 3 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D044085:Microfluidics; D009062:Mouth Neoplasms / Q000473:pathology*; D049329:Nanostructures; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C071894:DSG3 protein, human; D051184:Desmoglein 3