Koos Boeve

109 Cyclin D1 in early oral cancer mainly significant between normal copy number and high-level amplification, with adjusted p-value < 0.001. Normal copy number versus low-level amplification and low-level versus high-level amplification showed no significant differences in nuclear cyclin D1 expression, with adjusted p-values of 0.277 and 0.051, respectively. Table 2. Descriptive analysis Cyclin D1 FADD Cortactin Immunohistochemistry Cores per tumor (%) 0 1 2 3 6 (4%) 10 (6%) 43 (27%) 99 (63%) 4 (2%) 8 (5%) 25 (16%) 121 (77%) 6 (4%) 10 (6%) 22 (14%) 120 (76%) Intratumor Heterogeneity ICC (95% CI) 0.89 (0.84-0.92) 0.89 (0.85-0.92) 0.90 (0.86-0.92) Expression (%) normal overexpression missing 90 (57%) 62 (39%) 6 (4%) 124 (79%) 30 (19%) 4 (3%) 128 (81%) 24 (15%) 6 (4%) FISH Tumors (%) Normal copy number low-level amplification high-level amplification missing 97 (62%) 18 (11%) 24 (15%) 19 (12%) Abbreviations : FISH: fluorescence in situ hybridization, ICC: intraclass correlation coefficient Biomarker for (occult) nodal metastasis To address the value of CCND1 amplification and expression of cyclin D1, FADD and cortactin as potential biomarkers for occult nodal metastasis, we correlated amplification or overexpression with histologically proven nodal metastases. In early oral cancer, the NPV (i.e. true negative outcome in case of negative test result) varied between 79% and 85% among different biomarkers and techniques (see Table 3). Combination of protein expression of the three 11q13 oncogenes (cyclin D1, FADD and cortactin) slightly improved the NPV comparable with the NPV of cyclin D1 expression alone, 85% versus 84%.