title: Prognostic value of tissue and circulating levels of IMP3 in prostate cancer.
abstract: Tissue levels of the oncofetal protein insulin-like growth factor 2 (IGF2) messenger RNA-binding protein 3 (IMP3) have been associated with poor prognosis in multiple human malignancies. However, its circulating levels have not yet been analyzed. Therefore, the aim of this study was to assess the prognostic value of both serum and tissue levels of IMP3 in prostate cancer (PC). IMP3 protein expression was analyzed in 124 PC and 13 benign prostate hyperplasia (BPH) patients using immunohistochemistry. Gene expression levels of IMP3 and its molecular target IGF2 were analyzed in 29 frozen and 26 paraffin-embedded PC tissues using real-time polymerase chain reaction and immunohistochemistry. Serum IMP3 levels were assessed in 94 PC and 20 BPH patients as well as in 20 controls using enzyme-linked immunosorbent assay. IMP3 immunostaining was present in 0% (0/13) of BPHs, 15% (15/101) of clinically localized PCs and 65% (15/23) of palliatively treated metastatic PCs (p < 0.001). Accordingly, serum IMP3 concentrations were significantly higher in PC compared to BPH patients which were higher than those in controls (p < 0.001 each). The highest concentrations were detected in metastatic PC patients (p = 0.036). In patients who underwent radical prostatectomy high IMP3 serum levels were independently associated with poor cancer-specific survival. IMP3 gene and protein expressions were not correlated with those of IGF2. In conclusion, we found enhanced IMP3 levels in tissue and serum samples of PC patients compared to non-PC men. Moreover, IMP3 was associated with metastasis and PC-specific survival. The tumor promoting effect of IMP3 appears to be independent from its regulatory role on IGF2 in PC.
authors.affiliation: Department of Urology, Medical University Vienna, Vienna General Hospital, Wien, Austria.
authors.forename: Tibor
authors.initials: T
authors.lastname: Szarvas
authors.forename: Stephan
authors.initials: S
authors.lastname: Tschirdewahn
authors.forename: Christian
authors.initials: C
authors.lastname: Niedworok
authors.forename: Gero
authors.initials: G
authors.lastname: Kramer
authors.forename: Sabina
authors.initials: S
authors.lastname: Sevcenco
authors.forename: Henning
authors.initials: H
authors.lastname: Reis
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Herbert
authors.initials: H
authors.lastname: Rübben
authors.forename: Frank
authors.initials: F
authors.lastname: vom Dorp
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
keywords: IMP3; KOC; immunohistochemistry; prognosis; prostate cancer; serum