149 MET, ECD shedding, and loss of E-cadherin immunoreactivity. B. The medians for uniform positivity observed using D1C2 and uniform negativity observed using NCH-38 are identical (10.0%), implying that E-cadherin tends to be absent in uniform positive C-terminal MET cancer areas. C. The median for gradient toward the periphery using D1C2 (40.0%) is significantly lower than that observed for gradient toward the center using NCH-38 (70.0%), corresponding with the observation that C-terminal MET immunoreactivity is generally lower than E-cadherin immunoreactivity described under A. D. The median for uniform negativity observed using A2H2-3 (65.0%) is significantly higher than that observed using D1C2 (15.0%). E. The median for uniform positivity observed using A2H2-3 (5.00%) is significantly lower than that observed using D1C2 (10.0%). F. The median for gradient toward the periphery observed using A2H2-3 (20.0%) is significantly lower than that observed using D1C2 (40.0%). Evaluation of MET protein status and its association with patient prognosis Aligning the scores obtained for D1C2 and A2H2-3, reveals that 8.9% of the cancers (n = 18) are negative for – both C- and N-terminal – MET immunoreactivity, that 16.1% of the cancers (n = 33) show the decoy receptor in the gradient toward the periphery and/or uniform positive staining pattern, and that 74.9% of the cancers (n = 152) are positive for TM C-terminal MET in the gradient toward the periphery and/ or uniform positive staining pattern. Within the latter category, 19.7% of the cancers (n = 30) are not subjective to MET ECD shedding and 80.3% of the cancers (n = 122) are subjective to MET ECD shedding in the gradient toward the periphery and/or uniform positive staining pattern (Supplementary table 20). KM curves reveal that there is no difference in OS or DFS for patients diagnosed with cancers showing absence of MET immunoreactivity, the MET decoy receptor, or TM C-terminal MET (Supplementary figures 5A and B). Association of the staining patterns with patient prognosis in TM C-terminal MET-positive cancers ROC curve analyses show that the D1C2 uniform positive and the NCH-38 uniform negative staining patterns are associated with both OS and DFS if they comprise ≥10% of cancer cells (Supplementary figures 6 and 7 for D1C2 and Supplementary figures 8 and 9 for NCH-38). 5
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