62 Chapter 3 the poor prognosis of primary breast cancers (54), illustrates that our finding does not stand completely on its own. In addition to MET staining pattern, the prognostic value of clinico-pathological characteristics known to be associated with the survival of patients with HNSCC (55) was examined. The results revealed that clinical and histological T and N-stage, differentiation grade, vasoinvasive growth and extranodal growth are significantly associated with poor 5-year OS. With the exception of differentiation grade and vasoinvasive growth, the same parameters were also significantly associated with poor 5-year DFS. Subsequent multivariable analysis revealed an effect of MET staining pattern on survival that is dependent on the status of vasoinvasive growth. Where MET staining pattern significantly influences 5-year OS and DFS in patients lacking signs of vasoinvasive growth, it has no effect on survival in patients with vasoinvasive growth. Since other studies describe that the presence of vasoinvasive growth is significantly associated with cancer recurrence and poor prognosis of patients diagnosed with HNSSC (56, 57), we hypothesize that the effect of MET staining pattern on survival is subservient to that of vasoinvasive growth. Therefore, further multivariable survival analysis was restricted to patients lacking signs of vasoinvasive growth. Since MET staining pattern significantly contributes to the final multivariable models for 5-year OS and DFS, we suggest that MET staining pattern might be of added value in treatment decision-making for patients lacking signs of vasoinvasive growth. In conclusion, this study shows that using a specific and sensitive antibody directed against the C-terminus of MET, both scarce and abundant membranous MET immunoreactivity are significantly associated with poor survival rates of patients with oral and oropharyngeal SCC lacking signs of vasoinvasive growth. These findings might contribute to reliable stratification of patients eligible for treatment with biologicals directed against MET. Yet, whether patients suffering from cancers showing abundant membranous MET immunoreactivity could benefit from treatment with MET inhibitors needs further investigation.
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