197 MET and nodal metastasis probably be explained by the low number of cases with DOI ≤ 4mm. These results suggest that MET positivity might also be of value in predicting the presence or absence of occult LNM in the preoperative setting, and besides DOI, in the postoperative setting (after removal of the primary tumor) in early OTSCC. We foresee that performing routine immunohistochemistry using the D1C2 antibody against the C-terminus of MET on biopsies, could be of great value in deciding when and when not to perform an END during the initial OTSCC surgery. This would improve logistics, cost-effectiveness, and would reduce patient morbidity caused by two separate surgeries. This study is performed on whole tissue sections, therefore efforts have to be made to design a future study to extrapolate these results to biopsies. To anticipate for cancer heterogeneity we expect that (preoperative) biopsies will need to be taken from the center and periphery of the cancer (17). The fact that there were less occult LNMs for cancers negative for MET and with DOI ≤ 4 mm compared to cancers positive for MET and with DOI ≤ 4 mm, illustrates that MET positivity could be of added value to DOI ≤ 4 mm for the clinical decision on the treatment of the cN0 neck i.e., whether regular follow-up, watchful waiting, or END is more appropriate. We can imagine that patients with MET positive cancers and DOI ≤ 4 mm could have more stringent follow-up than patients in the same DOI group but with MET negative cancers. We realize that this statement is based on very low numbers and independent validation is necessary. Taking into account that the obtained results are preliminary and need to be independently validated in a larger and more recent patient cohort incorporating both patients that underwent END and watchful waiting and containing detailed registration of relevant histopathological parameters, we believe that MET positivity could be of added value in pre- and postoperative (after primary tumor resection) decision making on END in early OTSCC. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 6
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