242 Chapter 8 Conclusion Emphasizing that the results obtained in this thesis need to be independently validated in larger patient cohorts, it is concluded here that C-terminal MET uniform positivity and ECD shedding are associated with poor prognosis and might aid in the stratification of OSCC patients eligible for treatment with MET targeted therapies. Additionally, it is also concluded that C-terminal MET uniform positivity is associated with RLNM (pN+ and occult) in early OSCC and could facilitate clinical decision making on performing an END. Furthermore, we believe that, besides patient stratification in view of MET targeted therapies and clinical decision making on END, detection of MET, using immunohistochemistry or other molecular methods, can be valuable for other facets of healthcare that involve – improving – the management of patients diagnosed with OSCC. More specifically, we are referring to MET targeted fluorescence-guided surgery (77-79) that assesses resection margin status (80, 81), nodal involvement (82-84), and (micro)metastatic spread (85). The use of MET targeted therapies in the adjuvant setting to resolve resistance against radiotherapy, chemotherapy, and cetuximab (1, 86). Combined use of MET targeted therapies and immune checkpoint inhibitors to reinitiate an immune competent tissue micro-environment resulting in cancer cell death (30). As MET immunoreactivity might aid in predicting survival, disease progression, optimal treatment of the neck, resistance/response to – systemic – therapy, we foresee it taking a place in clinical decision making and patient counseling, ultimately improving shared decision making. Taking everything into consideration, we dare to state here that MET immunoreactivity is a valuable biomarker in the field of OSCC. Future perspective Having enumerated all potential benefits of MET detection, it should be mentioned that we do realize that the obtained results in this thesis do not provide any information about actual MET and/or MET-EC- functional activity - either at the membrane, cytoplasm, or nucleus - nor the effect of targeted therapies. As such, functional experiments investigating activity of MET and/or MET-EC-, and the effectiveness of targeted therapies in different contexts are necessary alongside the development of relevant CDx.
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