Increased insulin mRNA binding protein-3 expression correlates with vascular enhancement of renal cell carcinoma by intravenous contrast-CT and is associated with bone metastasis

Abstract

PurposeTo: 1) assess the correlation between CT vascularity and a candidate molecular marker of RCC metastasis (insulin-like mRNA binding protein-3 (IMP3)); and 2) demonstrate the differential expression of IMP3 in high vs. low vascular tumors. Experimental designRetrospectively obtained contrast CT from 72 patients with primary RCC were used to establish threshold values for Low, Intermediate and High tumor vascularity. Paired histopathology specimens from 33 of these patients were used for immunohistochemistry (IHC) to correlate CT with IMP-3 expression. IMP-3 gene expression studies were performed on RCC and poorly vascular prostate cancer (PC) human bone metastases samples to confirm presence of IMP3 in metastatic samples from RCC. Gene expression studies were performed on RCC 786-O and PC3 cell lines to confirm the presence of high expression of IMP3 in the RCC cell line. ResultsIMP-3 expression positively correlated with CT vascular enhancement (p<0.01). IMP3 expression by IHC was strongly positive in all RCC, but weak in PC bone metastases. Real time RT-PCR demonstrated a significant 4-fold increase in imp-3 expression in RCC 786-O vs. PC3 cells in vitro (p<0.001). ConclusionQuantitation of pre-operative CT is a feasible method to phenotype primary RCC vascularity, which correlates with IMP-3 expression. In situ and cell line studies demonstrate an association between high IMP-3 expression and RCC bone metastasis. Studies aimed at defining the diagnostic potential of biomarkers for RCC bone metastasis, and functional significance of IMP-3 in RCC vascularity and tumor progression are warranted.