189 MET and nodal metastasis Introduction Approximately one third of head and neck squamous cell carcinoma (HNSCC) originate in the oral cavity (OSCC) (1). For patients diagnosed with OSCC with clinically positive cervical lymph nodes, primary tumor resection with neck dissection is indicated. On the other hand, elective neck dissection (END) is recommended if the risk of occult lymph node metastasis (LNM) is 20% (2). To date, tumor depth of invasion (DOI) is an established predictor for occult LNM and is recommended by the NCCN in making decisions on END (1). Depth of invasion with a cut-off value (> 4 mm) is a strong predictor for occult LNM, this cutoff value is therefore used within the Erasmus MC in making decisions on END (1, 3, 4). The DOI however is determined during the final pathological evaluation, days after the excision of the primary tumor (5). Therefore, cancers with DOI of > 4 mm, would necessitate a second stage END resulting in additional morbidity for the patient, inefficient use of resources, time, and extra costs. Another downside of DOI is that it has been used interchangeably with tumor thickness, another predictor of LNM (6-9). This problem has been addressed in the 8th edition of the AJCC that provides a clear definition for DOI (5). In some centers, sentinel lymph node biopsy (SLNB) is being performed to rule out the presence of occult LNM. With detection rates of 95% (10-12), 0.93 sensitivity and NPV of 0.88 to 1 (11-15), SLNB is a reliable method to detect occult LNM during surgery. However, the success rate of SLNB depends on the experience and technical expertise of the team performing the procedure making the implementation of SLNB in routine patient care difficult (1). It is clear, that there still is a need for reliable preoperative predictors of occult LNM that can further improve the decision making process on END. Ideally, such predictors should be easily incorporated in a routine diagnostic setting. A target of interest is the receptor tyrosine kinase MET (16). Using a novel scoring system, it was shown that MET positivity is associated with poor overall survival (OS) and disease-free survival (DFS) in OSCC (17). Amongst its pleiotropic functions as an oncogene, MET orchestrates the program of invasive growth (16, 18, 19). As MET facilitates the dissemination of cancers cells, it is an interesting target for the prediction of LNM. 6
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