title: Relation of ETS transcription factor family member ERG, androgen receptor and topoisomerase 2β expression to TMPRSS2-ERG fusion status in prostate cancer.
abstract: Fusion of TMPRSS2 with ERG in prostate cells is determined by double-strand DNA breaks induced by androgen signaling and transcription stress. The enzyme topoisomerase 2β (TOP2B) mediating DNA processing, plays an important role in DNA cleavage. The aim of this study was to analyse expression of AR, TOP2B and ERG in relation to TMPRSS2-ERG gene rearrangement and relevant clinicopathological characteristics in prostate cancer (CaP). Immunohistochemical staining and FISH were used for investigation. ERG expression in prostate cell lesions positively correlated with levels of TMPRSS2-ERG fusion gene (p<0.0001). The most significant co-expression of ERG was found with AR in CaP (p=0.001). Significantly more frequent co-expression of ERG was also revealed with TOP2B (p=0.028). ERG protein expression did not correlate with CaP differentiation status as we found no significant differences in ERG expression for different Gleason categories. We demonstrated a statistically significant positive correlation between the percentage of cells with fusion gene TMPRSS2-ERG in CaP and metastatic potential of tumors (p=0.011). Besides these positive corelations of AR with ERG (p=0.001) and TOP2B with ERG (p=0.028), we also demonstrated a significant co-expression of AR with TOP2B (p=0.007) in CaP. There was a statistically significant increase in the TOP2B H-index in locally advanced CaP in comparison with localized tumors (p=0.046). ERG expression correlates with occurrence of TMPRSS2-ERG fusion and with AR-driven malignant transformation. The results indicate that detection of the TMPRSS2-ERG fusion gene and parallel immunohistochemical examination of AR, TOP2B and ERG has diagnostic significance and may be useful in assessing the biological character of the prostate cancer as well as selecting the best treatment.
authors.forename: Z
authors.initials: Z
authors.lastname: Kolar
authors.forename: A
authors.initials: A
authors.lastname: Burdova
authors.forename: T
authors.initials: T
authors.lastname: Jamaspishvili
authors.forename: J
authors.initials: J
authors.lastname: Bouchal
authors.forename: R
authors.initials: R
authors.lastname: Kucerova
authors.forename: M
authors.initials: M
authors.lastname: Bienova
authors.forename: M
authors.initials: M
authors.lastname: Kral
authors.forename: V
authors.initials: V
authors.lastname: Student
mesh_terms: D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis* / Q000502:physiology; D015534:Trans-Activators / Q000032:analysis*; D000071230:Transcriptional Regulator ERG
chemical_list: C410798:AR protein, human; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; D000075223:Poly-ADP-Ribose Binding Proteins; D011944:Receptors, Androgen; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D004250:DNA Topoisomerases, Type II; C000618814:TOP2B protein, human