HuR Regulates IGF1R Expression in Pancreatic Adenocarcinoma.
Mary J McDonald, Jessica Kline, Sufian Zaheer, Visahal Patel, Charles J Yeo, Jonathan Brody, Agnieszka K Witkiewicz. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Current therapy for pancreatic ductal adenocarcinoma (PDA) consists of surgery and/or gemcitabine-based chemotherapy. High expression of Hu protein antigen R (HuR) has been recently demonstrated to be a positive predictive marker for overall survival in patients with PDA receiving gemcitabine. In vitro, HuR has been shown to inhibit translation of type 1 insulin-like growth factor receptor (IGF1R), the overexpression of which is associated with invasiveness of PDA. In this study we correlated expression of IGF1R and HuR in PDA and with clincopathological features and patient survival.
Design: IGF1R and HuR expression was evaluated in 98 PDA cases by immunohistochemistry using anti-IGF1R (clone G11, Ventana Medical Systems,) and anti-HuR (clone sc-5261, Santa Cruz Technologies) antibodies. IGF1R was scored on a four-point scale (0, 1+, 2+, 3+) according to the system used for HER-2 evaluation. HuR cytoplasmic staining was scored as low or high as we previously published. For statistical analysis IGF1R scores were dichotomized as low (0-1) vs. high (2-3). Associations between PDA grade and T/N stages and IGF1R and HuR were analyzed using Fisher's exact test. Overall survival was analyzed using LogRank test and Cox proportional hazard model.
Results: High IGF1R expression was associated with low HuR cytoplasmic positivity (p=0.0085). High expression of IGF1R correlated with higher tumor grade (p=0.033) and high expression of HuR with higher tumor stage. Patients with high IGF1R and low HuR had longer overall survival (median 19.9 months for high IGF1R/low HuR and 15.2 months for lowIGF1R/high HuR), however this difference was not statistically significant.
Conclusions: Our results support in vitro data showing that HuR can repress IFG1R protein expression. This finding should have implications for anti-IGF1R based therapies.
Category: Liver & Pancreas
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 213, Tuesday Afternoon