152 Chapter 5 Prognostic value of NCH-38 uniform negativity Univariable survival analyses show that patients showing loss of NCH-38 (n = 84, 55.3%) perform significantly worse in terms of OS (HR = 2.21; 95% CI = 1.30 to 3.77; P = 0.004; Figure 3C) and DFS (HR = 1.90; 95% CI = 1.20 to 3.01; P = 0.007; Figure 3D). To test the independent value of NCH-38 uniform negativity for OS and DFS, multivariable analyses were performed correcting for age at diagnosis, pT, pN, extranodal extension, and degree of differentiation. The results show that uniform negativity of NCH-38 remains significantly associated with survival (HR = 2.53; 95% CI = 1.35 to 4.73; P = 0.004 for OS and HR = 2.13; 95% CI = 1.26 to 3.60, P = 0.005 for DFS; Table 3). Table 3: Multivariable analysis—in view of the NCH-38 uniform negative staining pattern—of overall survival and disease-free survival for patients having cancers that are positive for transmembranous C-terminal MET in the gradient toward the periphery and/or uniform positive staining pattern (n = 152). Variable Overall survival Disease-free survival HR 95% CI P-value HR 95% CI P-value Age at diagnosis* 1.42 1.14 – 1.77 0.002 1.36 1.11 – 1.65 0.003 pT ≥ 1 1.43 0.73 – 2.82 0.300 1.15 0.66 – 2.01 0.615 pN ≥ 2 2.76 1.36 – 5.59 0.005 2.10 1.10 – 4.01 0.024 Extranodal extension present 0.91 0.40 – 2.05 0.814 0.89 0.41 – 1.92 0.768 Poor – undifferentiated opposed to well – moderate 1.19 0.56 – 2.50 0.652 0.91 0.45 – 1.82 0.785 ≥ 10% of cancer cells show the NCH-38 uniform negative staining pattern 2.53 1.35 – 4.73 0.004 2.13 1.26 – 3.60 0.005 * The HR was based on 10 year intervals. Association of MET ECD shedding with patient prognosis in TM C-terminal MET-positive cancers ROC curve analyses show that MET ECD shedding within the D1C2 uniform positive staining pattern is associated with both OS and DFS, if it comprises ≥10% of cancer cells (Supplementary figures 10 and 11). Prognostic value of MET ECD shedding within the D1C2 uniform positive staining pattern Univariable survival analyses show that patients showing ECD shedding within the D1C2 uniform positive staining pattern (n = 66, 43.4%) perform significantly worse in terms of OS (HR = 2.30; 95% CI = 1.38 to 3.83; P = 0.001; Figure 3E) and DFS (HR = 1.87; 95% CI = 1.19 to 2.92; P = 0.006; Figure 3F). To test the independent value of ECD shedding within the D1C2 uniform positive staining pattern for OS and DFS,
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