Relative 8q gain predicts disease‐specific survival irrespective of the TMPRSS2‐ERG fusion status in diagnostic biopsies of prostate cancer

Abstract

Screening tools have greatly improved prostate cancer (PCa) detection, but the disease course is heterogeneous, and standard clinicopathological parameters do not fully discriminate aggressive from indolent tumors. To evaluate the prognostic value of the TMPRSS2-ERG fusion gene combined with chromosome arm 8q relative gain in diagnostic biopsies of PCa, we studied a consecutive series of 200 diagnostic needle biopsies from patients with 10-year disease-specific survival data. TMPRSS2-ERG fusion gene status and relative 8q gain were assessed by fluorescent in situ hybridization in whole formalin fixed paraffin-embedded biopsies. The TMPRSS2-ERG fusion gene was detected in 43.5% of PCa and was associated with lower Gleason score (P = 0.045), whereas relative 8q gain was present in 48% of PCa and was associated in high-Gleason score (P < 0.001). ERG rearrangement alone was not associated with clinical outcome, whereas relative 8q gain predicted worse disease-specific survival in PCa patients both with and without the TMPRSS2-ERG fusion gene (P < 0.001), independently of Gleason score, clinical stage, and treatment modality. We conclude that relative 8q gain in diagnostic needle biopsies is a poor prognostic factor independent of the TMPRSS2-ERG fusion gene status and of standard clinicopathological parameters.

Prostate Cancer Prognosis Defined by the Combined Analysis of 8q, PTEN and ERG

“…Five-micrometer-thick sections of formalin fixed, paraffin-embedded (FFPE) prostatectomy specimens were processed and hybridized as previously described [22], [23], [34]. For the relative 8q24 gain assessment, a commercial dual-color break-apart probe flanking MYC at 8q24 (ZytoVision, Bremerhaven, Germany) and a centromeric probe for chromosome 18 (CEP18) labeled with SpectrumAqua (Vysis, Downers Grove, IL, USA) were used, as previously described [22], [23], [34].…”

“…For the relative 8q24 gain assessment, a commercial dual-color break-apart probe flanking MYC at 8q24 (ZytoVision, Bremerhaven, Germany) and a centromeric probe for chromosome 18 (CEP18) labeled with SpectrumAqua (Vysis, Downers Grove, IL, USA) were used, as previously described [22], [23], [34]. Slides were counterstained with DAPI (Vector Laboratories, Burlingame, CA, USA) and fluorescent signals were captured in a Zeiss Axioplan fluorescence microscope (Zeiss, Oberkochen, Germany) coupled with a Cohu 4900 CCD camera using a Cytovision system version 7.4 (Leica Biosystems Richmond, Inc., USA).…”

“…Chromosomal 8q gain has been associated with tumors in advanced stage [20] and a worse clinical outcome [21]. We have previously shown that PCa with relative 8q gain is associated with poor disease-specific survival, independently of Gleason score (GS) [22] and TMPRSS2-ERG gene fusion status [23]. Relative 8q gain was also strongly predictive of BCR in radical prostatectomy (RP) treated patients, independently of GS and TNM stage [24], thus supporting the role of relative 8q gain as a biomarker for aggressive PCa.…”

Prognostic Histopathological and Molecular Markers on Prostate Cancer Needle-Biopsies: A Review

“…Many groups have analyzed the presence of TMPRSS2:ERG fusion or ERG protein expression in prostate cancer cohorts with variable outcome [80–92]. Barros-Silva et al used fluorescent in situ hybridization (FISH) to detect TMPRSS2-ERG rearrangement in a cohort of 200 biopsies and found an association with low PSA levels at diagnosis and low Gleason score [93]. In needle-biopsies immunohistochemical ERG detection can be used to discriminate prostate cancer from its mimickers, although the additional value to other markers such as p63, basal cell keratin 5, and AMACR is limited [92, 94–99].…”

“…c-MYC is amplified in approximately 70% of clinical prostate cancer [93, 110, 111]. Ribeiro et al found that patients with gain of MYC gene copy numbers in a group of 60 prostate cancer needle-biopsies using FISH were significantly at risk for disease-specific death [110].…”