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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 inimp-3expression in RCC 786-O vs. PC3 cells in vitro (p<0.001).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York, United States of America ; Center for Musculoskeletal Research, University of Rochester Medical and Dental School, Rochester, New York, United States of America ; Joint Orthopaedic Research Center of Zunyi Medical University & University of Rochester Medical Center (JCMR-ZMU & URMC), Zunyi Medical University, Zunyi, Guizhou, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Radiology, First Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, People's Republic of China.
authors.forename: Yaying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York, United States of America ; Center for Musculoskeletal Research, University of Rochester Medical and Dental School, Rochester, New York, United States of America ; Department of Orthopaedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York, United States of America ; Center for Musculoskeletal Research, University of Rochester Medical and Dental School, Rochester, New York, United States of America ; Department of Orthopaedics, Zhejiang Provincial People's Hospital, Hongzhou, Zhejiang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Jorge
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Orthopaedics, Zhejiang Provincial People's Hospital, Hongzhou, Zhejiang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Bi
authors.affiliation: Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York, United States of America ; Center for Musculoskeletal Research, University of Rochester Medical and Dental School, Rochester, New York, United States of America ; Joint Orthopaedic Research Center of Zunyi Medical University & University of Rochester Medical Center (JCMR-ZMU & URMC), Zunyi Medical University, Zunyi, Guizhou, People's Republic of China.
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.affiliation: Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York, United States of America ; Center for Musculoskeletal Research, University of Rochester Medical and Dental School, Rochester, New York, United States of America ; Joint Orthopaedic Research Center of Zunyi Medical University & University of Rochester Medical Center (JCMR-ZMU & URMC), Zunyi Medical University, Zunyi, Guizhou, People's Republic of China.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.affiliation: Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York, United States of America ; Center for Musculoskeletal Research, University of Rochester Medical and Dental School, Rochester, New York, United States of America.
authors.forename: Wakenda
authors.initials: W
authors.lastname: Tyler