100 Chapter 4 The latter suggests that if ectodomain shedding and regulated intramembrane proteolysis occur, it might be heterogeneous. Taking everything into consideration, it is concluded that using fresh frozen tissues there are cancers without C-terminal MET immunoreactivity (n = 4, 13%) and cancers positive for C-terminal MET immunoreactivity (n = 26, 87%). Within the latter group (positive for C-terminal p145β), about half are not subjective to ectodomain shedding and/or regulated intramembrane proteolysis (n = 12, 46%) while others are subjective to ectodomain shedding (n = 2, 8%), regulated intramembrane proteolysis (n = 1, 4%), or both (n = 11, 42%). Finally, it was examined whether ectodomain shedding can be detected in corresponding formalin-fixed paraffin-embedded tissues. Comparing D1C2 and A2H2-3 immunoreactivities observed across parallel slides, it can be concluded that ectodomain shedding can be detected using immunohistochemistry and that it occurs in 50% (n = 15) of the examined cancers (Fig. 5b). Figure 5b also shows that 13 cancers are subjective to ectodomain shedding according to western blotting and 15 cancers are subjective to ectodomain shedding according to immunohistochemistry, showing an overlap of eight cases. A representative ectodomain shedding area observed using immunohistochemistry is depicted in Supplementary Fig. 3. All cancers subjective to shedding were positive for D1C2 (Supplementary Fig. 4). General results tissue microarray The intraclass correlation coefficient for the center cores was 0.88 (95% CI, 0.84– 0.91) and for the periphery cores was 0.87 (95% CI, 0.82–0.91). This indicates optimal agreement for both regions. Evaluation of average membranous D1C2 and A2H2-3 immunoreactivity in both cancer regions (center and periphery) was possible for 156 oral squamous cell carcinoma. The baseline characteristics of these cancers are indicated in Table 2.
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