Journal
ORAL ONCOLOGY
Volume 49, Issue 2, Pages 93-101Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.oraloncology.2012.08.001
Keywords
DSG3; Head and neck cancer; Desmosomes; Biomarker; Sentinel lymph nodes; Nanosensors; Immunoarray; Lymph nodes metastasis; Proteomics; SCC
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Funding
- Intramural Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering [R01EB014586]
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Objectives: 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. Materials and 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. Conclusion: 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. Published by Elsevier Ltd.
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