Abstract 2254: Nuclear and cytoplasmic epidermal growth factor receptor and p16 expression as prognostic biomarkers in head and neck squamous cell carcinoma
Authors: Hatim Husain, Amanda Psyrri, Robbert Slebos, Douglas T. Ross, Barbara Burtness, Christine H. Chung
Journal: Cancer Research (2011)

Abstract Introduction: Epidermal growth factor receptor (EGFR) and p16 staining have demonstrated to be strong prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC). Patients with higher expression of EGFR in their tumors have been correlated with decreased survival and shorter time to recurrence. Patients with p16-positive (+) tumors [a surrogate marker of human papillomavirus (HPV) infection] have improved survival compared to p16-negative (−) tumors. We examined the interaction between the expression levels of total EGFR and p16 status, and further examined the association between nuclear EGFR and p16 status based on evidence that nuclear EGFR may have a distinct role in DNA damage repair and may function as a transcription factor. Methods: A tissue microarray (TMA) containing 123 cores obtained from 101 HNSCC tumors was analyzed for EGFR expression (clone H11; DAKO, Carpinteria, CA) using an automated quantitative analysis (AQUA), and for p16 expression (clone E6H4; MTM Laboratories Inc., Westbrough, MA) using immunohistochemical (IHC) staining. Duplicate cores from a patient were averaged for analyses. The EGFR and p16 data were correlated with clinical data including demographics, primary subsite, disease stage, and survival. Results: The total and nuclear EGFR data could be reliably obtained from 80 of 101 patients. The p16 data could be obtained from 87 of 101 patients [p16 (+), n=29; p16 (−), n=58]. The p16 staining was strongly associated with the oropharyngeal subsite (Chi2, p=&amp;lt;0.0001) and poorly differentiated histology (Cochran-Armitage Trend Test, p=0.01). The expression of total and nuclear EGFR was higher in p16 (−) tumors compared to p16 (+) tumors (Wilcoxon Rank Test, p=0.038 and p=0.014, respectively). Interestingly, the higher expression of non-nuclear EGFR (combined cytoplasmic and membranous) staining did not associate significantly with p16 (−) tumors. Statistically significant differences in recurrence-free survival or overall survival were not detectable based on the EGFR and p16 expression, likely due to the small sample size and heterogeneity in the patient population. Conclusions: The total and nuclear EGFR expression levels were higher in p16 (−) tumors compared to p16 (+); this may relate to recurrence and poor survival. Additionally, localization of EGFR may be a significant factor in its association with clinical outcomes. Further studies are indicated to determine the mechanistic link between these two prognostic factors and define the significance of EGFR localization to nucleus upon activation of the pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2254. doi:10.1158/1538-7445.AM2011-2254