Insulin-Like Growth Factor-2 mRNA Binding Protein 3 (IGF2BP3) Expression May Be a Marker for a Unfavorable Prognosis in Pancreatic Ductal Adenocarcinoma
DF Schaeffer, D Owen, HJ Lim, E Mehl, AK Buczkowski, SW Chung, CH Scudamore, DA Owen, SSW Ng, DG Huntsman. The University of British Columbia, Vancouver, BC, Canada; BC Cancer Agency, Vancouver, BC, Canada
Background: Pancreatic adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in advanced stages. In this setting therapeutic markers identifying aggressive tumors, could aid in management decisions. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3, also known as IMP3 or KOC) is an oncofetal RNA-binding protein regulating targets such as insulin-like growth factor 2 (IGF2) and ACTB (beta-actin) and has previuosly been demonstrated to be expressed in pancreatic adenocarcinoma.
Design: The expression of IGF2BP3 was evaluated by immunohistochemistry on a tissuemicroarray of 128 pancreatic adenocarcinoma with tumor grade 1, 2 and 3, according to WHO criteria. Non-neoplastic pancreatic parenchyma served as control tissue. Slides were reviewed by two pathologists, blinded to clinical outcome, and scored. Cut-off point for positive cases was any convincing cytoplasmic expression in more than 5% of tumor cells. Univariate disease specific survival analysis was performed by the generation of Kaplan- Meier curves and differences assessed with the log-rank statistic. Multivariable disease specific survival analysis was assessed with the Cox proportional hazards regression model.
Results: IGF2BP3 was found to be selectively overexpressed in pancreatic ductal adenocarcinoma tissues but not in benign pancreatic tissues, as previously reported. 9 (40%) patient samples of tumor grade 1 (n=24) and 27 (44%) of tumor grade 2 did express IGF2BP3. The highest rate of expression was seen in poorly differentiated specimen (Grade 3, n=42) with 26 (63%) positive samples. Overall survival was found to be significantly shorter in patients with IGF2BP3 expressing tumors (p=0.001; RR 2.3, 95% 1.2-4.8).
Conclusions: Although IGF2BP3 is expressed in a variety of malignant neoplasm (i.e. pulmonary SCC, ovarian CCC and RCC) prognostic value has only be demonstrated in RCC. Our data suggest, that IGF2BP3 denotes a subset of pancreatic adenocarcinomas with an extremly poor outcome and provides a rationale for developing therapies to target the IGF pathway in this cancer.
Category: Liver & Pancreas
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 235, Wednesday Morning