156 Chapter 5 Figure 4: Proposed stratification scheme for OSCC eligible or not eligible for targeted therapies directed against MET. The developed scoring system characterizes D1C2, A2H2-3, and NCH-38 immunoreactivity across cancer sections in the form of staining patterns (uniform negative or positive and gradient toward the periphery or center). By aligning D1C2, A2H2-3 and/ or NCH-38 staining patterns, it also facilitates investigation of MET protein status and biological processes such as MET ECD shedding and EMT. Finally, it establishes an independent association of D1C2 uniform positivity, ECD shedding, and loss of E-cadherin with poor OS and DFS. Ultimately, the findings concerning MET immunoreactivity and ECD shedding might support the development of CDx for targeted therapies directed against the RTK MET or orchestrators of shedding. Acknowledgements We thank all the head and neck surgeons of the Leiden University Medical Center (LUMC) for facilitating the use of their resection specimens and follow-up data. The authors also thank Prof. dr. Vincent Smit for his guidance and critical feedback. Finally, the authors also thank the past and present members of the Clinical Diagnostics Laboratory at Eli Lilly and Company for technical assistance.
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