Abstract 5729: Loss of USP10 and p14ARF protein expression is associated with poor prognosis patients with small intestinal adenocarcinoma

Abstract

Abstract Ubiquitin Specific Peptidase 10 (USP10) is a member of the ubiquitin-specific protease family and its related pathways are apoptosis, autophagy and DNA damage. P14ARF is encoded by an alternative reading frame within the INK4a/ARF locus at chromosome 9p21, which is related with cell cycle arrest and apoptosis. Recently, ablation of USP10 prevented c-myc induced cellular senescence by destabilization of p14ARF and p53, and accelerated hyper-proliferation and transformation of normal cells, suggesting USP10 have a crucial role in oncogenes induced senescence by keeping the stability of p14ARF and p53, key regulator of cellular senescence. However, knowledge on the clinical and prognostic significance of USP10 and p14ARF expression in patients with small intestine adenocarcinoma is limited. In the present study, we investigated the prognostic significance of USP10 and p14ARF by immunohistochemistry. 195 of resected small intestine adenocarcinomas were retrieved from 22 South Korean institutions by Korean Small Intestinal Cancer Study Group. Tissue microarrays were constructed using formalin-fixed paraffin-embedded specimen. 70 (35.9 %) out of 195 patients showed immunoreactivity for USP10 and 124 (63.6 %) showed loss of immunoreactivity for USP10. 120 (61.5 %) of 195 patients were immunopositive for p14ARF and 75 (38.5 %) patients showed loss of immunoreactivity for p14ARF. Loss of USP 10 was correlated with male predominancy (p=0.014), higher pT stage (p=0.044), presence of lymphatic invasion (p=0.033), absences of sporadic adenoma (p=0.024) and absences of peritumoral dyplasia (p=0.019). On multivariate survival analysis, loss of USP10 expression was independent poor prognostic factor ( HR=3.04, 95% CI= 1.79-5.18, p < 0.001) and also both loss of USP10 and p14ARF expressions showed similar result ( HR=3.76, 95% CI= 1.93-7.23, p < 0.001) while loss of p14ARF was not an independent prognostic factor ( p= 0.587). Our findings indicate that loss of USP10, associated with loss of p14ARF protein expression, could be poor prognostic factors in small intestine adenocarcinoma. Citation Format: Joon Seon Song, Hanbyoul Cho, Joon-Yong Chung, Ilseon Hwang, Hee Jin Lee, Seung-Mo Hong, Stephen M. Hewitt. Loss of USP10 and p14ARF protein expression is associated with poor prognosis patients with small intestinal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5729. doi:10.1158/1538-7445.AM2017-5729