Abstract
Prostate cancer (PCa) is a very heterogeneous disease, and there are constraints in its current diagnosis. Serum PSA levels, digital rectal examination (DRE), and histopathologic analysis often drive to overdiagnosis and overtreatment. Since 2005, the presence of the genetic rearrangement between transmembrane-serine protease gene (TMPRSS2) and the erythroblast transformation-specific (ETS) member ERG (v-ets erythroblastosis virus E26 oncogene homolog avian) has been demonstrated in almost half of PCa cases. Both FISH and RT-PCR are useful tools for detecting these rearrangements, but very few comparatives between both techniques have been published. In this study, we included FFPE tumors from 294 PCa patients treated with radical prostatectomy with more than 5 years of followup. We constructed a total of 20 tissue microarrays in order to perform break-apart and tricolor probe FISH approaches that were compared with RT-PCR, showing a concordance of 80.6% (P < 0.001). The presence of TMPRSS2-ERG rearrangement was observed in 56.6% of cases. No association between TMPRSS2-ERG status and clinicopathological parameters nor biochemical progression and clinical progression free survival was found. In conclusion, this study demonstrates that both FISH and RT-PCR are useful tools in the assessment of the TMPRSS2-ERG fusion gene status in PCa patients and that this genetic feature per se lacks prognostic value.
Highlights
Prostate cancer (PCa) is a heterogeneous disease, which ranges from indolent to lethal behaviour [1]
Formalin fixed and paraffin-embedded (FFPE) blocks corresponding to PCa patients were retrieved from the archives of the Biobank of the Fundacion Instituto Valenciano de Oncologıa according to the following criteria: radical prostatectomy specimens and no history of previous treatment for PCa
Since the three-color assay is a novel approach for TMPRSS2ERG analysis, a break-apart fluorescence in situ hybridization (FISH) was first conducted in two tissue microarrays (TMAs) including 38 cases in order to validate the tricolor Kreatech probes
Summary
Prostate cancer (PCa) is a heterogeneous disease, which ranges from indolent to lethal behaviour [1]. The diagnosis may be clinically suspect based on an elevated serum prostate specific antigen (PSA) and/or abnormal digital rectal examination (DRE), the definitive diagnosis established by histopathologic examination of needle biopsy tissue Both PSA and DRE often lead to both overdiagnosis and overtreatment presenting limitations when differentiating between indolent and aggressive PCa [2]. Biopsy is far from being optimal because it has demonstrated a lack of sensitivity and high risk of morbidity for patients [3] In this context, there is an increasing demand of specific biomarkers for PCa diagnosis that provides information regarding the prognosis of the disease. The main mechanisms by which the TMPRSS2-ERG fusion genes are produced are interstitial deletion and balanced translocation [9] Because of their specificity, detection of these fusion genes could be a valuable ancillary diagnostic tool in the early detection of PCa [10]. These rearranged genes can be detected either by fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR) techniques [7, 11,12,13,14], or branched DNA (bDNA) analysis that is a very sensitive approach [15]
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