DSG3 as a biomarker for the ultrasensitive detection of occult lymph node metastasis in oral cancer using nanostructured immunoarrays

Abstract

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 (TMA), 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.

The genetic landscape of anaplastic astrocytoma

“…We found DSG3 mutated in 19% of A3s, all of which do not harbor the IDH1 mutation. DSG3 has been reported to be expressed at high levels in head and neck squamous cell carcinoma, and has been implicated as a potential biomarker for detection of this cancer's lymph node metastases [24]. Furthermore, within A3s we identified frequent mutations (5/16, 31%) in members of the Notch pathway ( NOTCH1 , NOTCH2 , NOTCH4 , NOTCH2NL ).…”

Determining the potential of desmoglein 3 as a sensitive and specific immunohistochemical marker for the detection of micrometastasis in patients with primary oral squamous cell carcinoma

“…Reticulum cells, ectopic salivary gland inclusions, mesothelial inclusions, and metastatic thyroid follicles can show cytokeratin positivity [12, 14]. Several studies have also found inconsistencies in the precise cytokeratin to be analysed [7]. …”

“…The importance of DSG3 as a novel molecular target for the early detection, prevention, and treatment of HNSCC was demonstrated in the higher expression of DSG3 in the proteomic analysis of HNSCC lesions by Patel et al . (2008) [7]. …”

“…In 2013, Patel et al identified DSG3, from amongst an array of other markers, to be a squamous-specific protein marker expressed specifically in the positive lymph nodes and a potential marker for detecting micrometastatic deposits [7]. This study tested the potential of DSG3 for the detection of micrometastasis in the cervical lymph nodes of patients with primary HNSCC.…”

Prognostic and Predictive Protein Biomarkers in Laryngeal Squamous Cell Carcinoma—A Systematic Review

“…Biomarkers, such as desmoglein 3 and Tissue-Specific Mir-205, have been shown to be associated with metastatic head and neck cancer and hence have the potential to be diagnostic biomarkers for this condition [7] [8].…”