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

Purpose: To: 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 design: Retrospectively obtained contras...

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Main Authors: Chao Xie, Yaying Li, Qingqing Li, Yu Chen, Jorge Yao, Guoyong Yin, Qing Bi, Regis J. O’Keefe, Edward M. Schwarz, Wakenda Tyler
Format: Article
Language:English
Published: Elsevier 2015-09-01
Series:Journal of Bone Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S221213741530018X
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author Chao Xie
Yaying Li
Qingqing Li
Yu Chen
Jorge Yao
Guoyong Yin
Qing Bi
Regis J. O’Keefe
Edward M. Schwarz
Wakenda Tyler
author_facet Chao Xie
Yaying Li
Qingqing Li
Yu Chen
Jorge Yao
Guoyong Yin
Qing Bi
Regis J. O’Keefe
Edward M. Schwarz
Wakenda Tyler
author_sort Chao Xie
collection DOAJ
description Purpose: To: 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 design: Retrospectively 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. Results: IMP-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). Conclusion: Quantitation 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.
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spelling doaj.art-ad60ab02600a49f6becc7ee879a166dc2022-12-21T23:42:56ZengElsevierJournal of Bone Oncology2212-13742015-09-0143697610.1016/j.jbo.2015.07.001Increased insulin mRNA binding protein-3 expression correlates with vascular enhancement of renal cell carcinoma by intravenous contrast-CT and is associated with bone metastasisChao Xie0Yaying Li1Qingqing Li2Yu Chen3Jorge Yao4Guoyong Yin5Qing Bi6Regis J. O’Keefe7Edward M. Schwarz8Wakenda Tyler9Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Radiology, First Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, People's Republic of ChinaDepartment of Orthopaedics, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Orthopaedics, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Pathology, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Orthopaedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of ChinaDepartment of Orthopaedics, Zhejiang Provincial People's Hospital, Hongzhou, Zhejiang, People's Republic of ChinaDepartment of Orthopaedics, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Orthopaedics, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Orthopaedics, University of Rochester Medical Center, Rochester, NY, United StatesPurpose: To: 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 design: Retrospectively 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. Results: IMP-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). Conclusion: Quantitation 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.http://www.sciencedirect.com/science/article/pii/S221213741530018X
spellingShingle Chao Xie
Yaying Li
Qingqing Li
Yu Chen
Jorge Yao
Guoyong Yin
Qing Bi
Regis J. O’Keefe
Edward M. Schwarz
Wakenda Tyler
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
Journal of Bone Oncology
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://www.sciencedirect.com/science/article/pii/S221213741530018X
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