Abstract 62: Loss of PERP p53/p63 target gene may indicate tumorigenesis at the margin and local recurrence

Abstract

Abstract Objectives: PERP (p53 apoptosis effector related to PMP22) localizes to the desmosomal adhesion complexes and is involved in suppressing squamous cell carcinoma (SCC) development. Loss of PERP expression leads to destabilization of desmosome complexes, resulting in enhanced tumor aggressiveness and worse local control in head and neck SCC (HNSCC). We had previously examined PERP loss at surgical margins in a small cohort of HNSCC patients. Results suggested that the loss of PERP may serve as a marker for persistent tumor and predictive of local relapse. Here we validate these findings in an independent patient cohort and report on the combined results of both groups. Materials and Methods: We previously examined the PERP protein expression by immunohistochemistry (IHC) in the surgical mucosal margins of 17 HNSCC patients. The validation cohort consists of 31 patients (15 oral cavity, 11 hypopharynx, 5 larynx). PERP expression was similarly assessed by IHC in the surgical margins of these patients. Finally, we combined the results of both groups to yield 48 patients with HNSCC (18 oral cavity, 12 hypopharynx, 4 oral pharynx, 14 larynx) for competing risk analysis. The relationship between local relapse and PERP expression (positive or negative) was analyzed in a competing risk model with death as a competing risk. Results: In the initial cohort, the 2-year cumulative incidence rate of local relapse was 37.5% for the negative PERP group compared to a 20% for the positive PERP group (p = 0.177). In the validation cohort, the 2-year cumulative incidence rate of local relapse was 50% for the negative PERP group compared to a 15% for the positive PERP group (p = 0.063). Since the results were similar between two groups, we combined them together for additional analyses. In this combined dataset, PERP expression was negative in 18, positive in 26, and not assessable in three patients. Of the 45 analyzable patients, the 2-year cumulative incidence rate of local relapse was 44.4% for the negative PERP group compared to a 16.4% for the positive PERP group (p = 0.010). There was also a trend for worse progression-free survival (p = 0.059) and overall survival (p = 0.085) with the loss of PERP. Conclusions: PERP loss at the surgical margins appears to be associated with a higher risk of local recurrence in HNSCC. These promising results need to be tested in a larger prospective study. Citation Format: Amanda Simmons, Christina Kong, Rie von Eyben, Laura Attardi, Xiaohui Ma, Quynh-Thu Le, Cherie-Ann Nathan. Loss of PERP p53/p63 target gene may indicate tumorigenesis at the margin and local recurrence [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 62.