Abstract
BackgroundPancreatic ductal adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in an advanced stage. In this setting, prognostic markers identifying the more agrressive tumors could aid in managment decisions. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3, also known as IMP3 or KOC) is an oncofetal RNA-binding protein that regulates targets such as insulin-like growth factor-2 (IGF-2) and ACTB (beta-actin).MethodsWe evaluated the expression of IGF2BP3 by immunohistochemistry using a tissue microarray of 127 pancreatic ductal adenocarcinomas with tumor grade 1, 2 and 3 according to WHO criteria, and the prognostic value of IGF2BP3 expression.ResultsIGF2BP3 was found to be selectively overexpressed in pancreatic ductal adenocarcinoma tissues but not in benign pancreatic tissues. Nine (38%) patient samples of tumor grade 1 (n = 24) and 27 (44%) of tumor grade 2 (n = 61) showed expression of IGF2BP3. The highest rate of expression was seen in poorly differentiated specimen (grade 3, n = 42) with 26 (62%) positive samples. Overall survival was found to be significantly shorter in patients with IGF2BP3 expressing tumors (P = 0.024; RR 2.3, 95% CI 1.2-4.8).ConclusionsOur data suggest that IGF2BP3 overexpression identifies a subset of pancreatic ductal adenocarcinomas with an extremely poor outcome and supports the rationale for developing therapies to target the IGF pathway in this cancer.
Highlights
Pancreatic ductal adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in an advanced stage
Patients and tumor specimens The expression of IGF2BP3 and insulin-like growth factor-2 (IGF-2) was evaluated by immunohistochemistry on a tissue microarray of 127 pancreatic adenocarcinoma, ranging from tumor grade 1, 2 and 3, from patients who underwent surgical resection at Vancouver General Hospital
IGF2BP3 expression pattern and survival IGF2BP3 is selectively overexpressed in pancreatic ductal adenocarcinoma tissues but not in benign pancreatic tissues, consistent with previous reports [14,15]
Summary
Pancreatic ductal adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in an advanced stage In this setting, prognostic markers identifying the more agrressive tumors could aid in managment decisions. IGF2BP3 was first cloned from a pancreatic tumor cDNA screen and was originally designated as KOC (KH-domain containing protein overexpressed in cancer) [5] It is known as an oncofetal protein because its expression is highest during embryogenesis [6,7,8,9,10], and is completely silenced in normal adult mouse tissues and is almost so in normal adult human tissues (with fibroblasts, lymphocytes, and the testes being the exceptions) [10,11]. The objective of the present study was to determine if expression of IGF2BP3 correlates with patient prognosis
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