Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) overexpression in pancreatic ductal adenocarcinoma correlates with poor survival.
BACKGROUND
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 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 that regulates targets such as insulin-like growth factor-2 (IGF-2) and ACTB (beta-actin).


METHODS
We 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.


RESULTS
IGF2BP3 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).


CONCLUSIONS
Our 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.
Schaeffer
David F
DF
Department of Pathology, The University of British Columbia, Vancouver BC, Canada. david.schaeffer@web.de
Owen
Daniel R
DR
Lim
Howard J
HJ
Buczkowski
Andrew K
AK
Chung
Stephen W
SW
Scudamore
Charles H
CH
Huntsman
David G
DG
Ng
Sylvia S W
SS
Owen
David A
DA
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
D000199:Actins; D018972:Insulin-Like Growth Factor Binding Protein 3; D007335:Insulin-Like Growth Factor II