Abstract
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous cancer that arises in the upper aerodigestive tract. Despite advances in knowledge and treatment of this disease, the five-year survival rate after diagnosis of advanced (stage 3 and 4) HNSCC remains approximately 50%. One reason for the large degree of mortality associated with late stage HNSCC is the intrinsic ability of tumor cells to undergo locoregional invasion. Lymph nodes in the cervical region are the primary sites of metastasis for HNSCC, occurring before the formation of distant metastases. The presence of lymph node metastases is strongly associated with poor patient outcome, resulting in increased consideration being given to the development and implementation of anti-invasive strategies. In this review, we focus on select proteins that have been recently identified as promoters of lymph node metastasis in HNSCC. The discussed proteins are involved in a wide range of critical cellular functions, and offer a more comprehensive understanding of the factors involved in HNSCC metastasis while additionally providing increased options for consideration in the design of future therapeutic intervention strategies.
Highlights
The main cause of cancer-related death is due to metastasis of primary tumors to secondary sites within the body
We focus on various studies conducted within the past four years that have linked overexpression of specific proteins in head and neck squamous carcinoma (HNSCC) to lymph node metastasis, highlighting several new potential candidates (Table 1) that could prove useful in the prediction, detection and treatment determination of metastatic disease
This study found that gene amplification correlated significantly to mRNA and protein expression, with cases containing strong cortactin staining significantly associated with lymph node metastasis
Summary
The main cause of cancer-related death is due to metastasis of primary tumors to secondary sites within the body. Several proteins involved in cell cycle regulation have recently been identified as markers with increased expression in HNSCC that correspond with lymph node metastasis. An increase in NBS1 expression in HNSCC regardless of origin site was associated with lymph node involvement [43] In this same study, NBS1 was found to be a prognostic marker even with samples divided into subgroups based on tumor and nodal stage or treatment type. Earlier studies by the authors had linked NBS1 overexpression to more aggressive disease and worse prognosis in advanced HNSCC [44], and to lymph node and distant metastasis [45] These studies determined NBS1 expression to be involved in cellular transformation through activation of the PI3K/Akt pathway and induction of EMT [44,45]. Identifying high risk patients through detection of NBS1 SNPs may be a useful tool in predicting patient outcome in OSCC and other HNSCC subtypes
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