49 MET immunoreactivity and poor prognosis Two observers (SW and MDH) independently assessed the percentage of MET positive cancer cells for each tissue core (Supplementary Figure S1E). Agreement was evaluated by means of a Bland and Altman diagram (Supplementary Figure S1F). In case of discordant scores, both observers simultaneously reassessed their counts after deliberation (Supplementary Figure S1G). If more than one core was available for evaluation per cancer region (center and periphery, see patient material), the average percentage of MET positive tumor cells was calculated. Evaluation of MET immunoreactivity in both cancer regions was possible in 183 out of the 240 tumors (76.3%) that are represented on the TMA (see patient material). Of these 183 tumors, only 4 oropharyngeal SCC were HPV-16 positive. Seen the low number, HPV-16 positive tumors were omitted from further analysis. The remaining patient population (n = 179) – evaluated for MET immunoreactivity in both the center and periphery – consisted of 114 males (63.7%) and comprised 131 advanced stage (III-IV) cancers (73.2%). Further baseline characteristics are indicated in Table 2. To investigate the consistency of MET immunoreactivity within the cancer center and periphery, we analyzed the Intraclass Correlation Coefficient (ICC) between the three scored cores per tumor region. The ICC is a descriptive statistic which describes how strongly different quantitative measures resemble each other, in this case multiple cores of the same tumor. An ICC < 0 reflects ‘poor’, 0 to 0.20 ‘slight’, 0.21 to 0.4 ‘fair’, 0.41 to 0.60 ‘moderate’, 0.61 to 0.8 ‘substantial’, and above 0.81 ‘almost perfect’ reliability of the measurement. Any measure should have an ICC of at least 0.6 to be useful with regard to reliability of the result. The 95% confidence intervals were indicated between brackets. Calculations were done with SPSS Statistics (version 21; IBM; Armonk, New York). Survival analysis Overall survival (OS) was defined as the time in months from the date of primary surgery to: the date of death due to any cause or the cutoff time (set at 60 months). Disease free survival (DFS) was defined as the time in months from the date of primary surgery to: the date of first evidence of any disease (local, regional, distant or secondary primary) progression, the date of death due to any cause or the cutoff time (set at 60 months). Individuals who were: lost to follow-up or survived beyond the cutoff time, were considered as censored observations. MET immunoreactivity OS as well as DFS curves were calculated by means of the Kaplan-Meier method and significance of differences in survival times was assessed with the log-rank test. Uni3
RkJQdWJsaXNoZXIy MTk4NDMw