Correlation of Prognostic Biomarkers, CD44 and EGFR, with Measures of Cellular Kinetics in P16 Negative Head and Neck Squamous Cell Carcinomas

p16 negative head and neck squamous cell carcinomas (HNSCCs) have a poorer prognosis and are less responsive to conventional therapies than their p16 positive counterparts. Our own prior work has shown a correlation between CD44 expression and p16 expression in human HNSCCs, and an association between CD44 and EGFR and poor survival. While CD44 and EGFR are each linked to multiple cellular functions, they both play a role in cell growth and cell cycle regulation. We sought to test the hypothesis that CD44 and EGFR are linked to increased cellular proliferation in p16 negative HNSCCs by correlating their expression with in vivo cellular kinetics measures. A TMA was created using tissue samples from 114 HNSCC patient enrolled on a prior clinical trial, T92-0045, which examined the role of proliferation measured by potential doubling time in patients receiving conventional radiotherapy throughout several centers in Europe. All patient samples and clinical outcomes were previously de-identified. Protein expression was assessed through immunohistochemistry (IHC) and quantified visually and using Definiens Tissue Studio software to generate histological scores, combining percent positivity and intensity. Measures of cellular kinetics included potential doubling time (Tpot), as calculated and reported by the T92-0045 clinical trial, as well as Ki67, which was assessed by IHC of the TMA generated in this study. Effects of biomarker expression, Tpot, and Ki67 on progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazard modeling for univariate analysis. Biomarker expression levels and measures of cellular kinetics were correlated with one another using the Pearson rank correlation. On univariate analysis, Ki67 and Tpot were statistically significant predictors of OS and PFS, however with hazard ratios at or near to 1 these were not clinically meaningful predictors. Table 1 shows correlation between biomarkers and measures of cellular kinetics: there was a significant negative correlation between Ki67 and Tpot and a significant positive correlation between Ki67 and EGRF. By showing significant negative correlation between Ki67, a marker of proliferation, and Tpot, which is considered a “gold standard” in vivo measurement of cellular proliferation, this study this confirms the utility of Ki67 as a measure of tumor proliferation. Furthermore, the correlation shown between EGFR and Ki67 underscores the potential role of EGFR in tumor cell proliferation and sheds light on a possible mechanism linking EGFR expression to poor prognosis in HNSCC.Abstract 3140; Table 1Pearson’s correlationEGFRCD44Ki67TpotEGFR-CD440.081 (p = 0.426)-Ki670.199 (p = 0.047)0.035 (p = 0.732)-Tpot-0.108 (p = 0.285)0.163 (p = 0.104)-0.254 (p = 0.010)- Open table in a new tab