A novel immunohistochemical scoring system reveals associations of C-terminal MET, ectodomain shedding, and loss of E-cadherin with poor prognosis in oral squamous cell carcinoma

• DOI: 10.1016/j.humpath.2020.07.018
• Publication Date: 2020-07-20T14:49:35Z
• Authors: Maria J. De Herdt; Senada Koljenović; Berdine van der S...; Stefan M. Willems; Marjan H. Wieringa; Daan Nieboer; Jose A. Hardillo; Aaron M. Gruver; Wei Zeng; Ling Liu; Robert J. Baatenb...; Leendert H.J. Loo...
• Keywords: Ectodomain

Using tissue microarrays, it was shown that membranous C-terminal MET immunoreactivity and ectodomain (ECD) shedding are associated with poor prognosis in oral cancer. Seen the potential diagnostic value, extrapolation of these results to whole-tissue sections investigated. Because orchestrates epithelial-to-mesenchymal transition (EMT), were benchmarked loss E-cadherin, a readout for EMT known be prognosis. MET, N-terminal E-cadherin immunoreactivities examined on formalin-fixed paraffin-embedded parallel 203 cancers using antibody clones D1C2, A2H2-3, NCH-38. Interantibody intra-antibody relations novel scoring system, nonparametric distribution, median tests. Survival analyses used examine prognostic value observed immunoreactivities. Assessment three revealed protein status (no, decoy, transmembranous positive), ECD shedding, EMT. For MET-positive cancers, D1C2 is independently overall survival (hazard ratio [HR] = 2.40; 95% confidence interval [CI] 1.25 4.61; P 0.008) disease-free (HR 1.83; CI 1.07-3.14; 0.027). both measures, this also case (43.4%, HR 2.30; 1.38 3.83; 0.001 versus 1.87; 1.19-2.92; 0.006) (55.3%, 2.21; 1.30 3.77; 0.004 1.90; 1.20-3.01; 0.007). The developed system accounts status, prognostically informative. These findings may contribute development companion diagnostics MET-based targeted therapy.